#molecular docking

[cbirt]

Small molecule drug discovery could be revolutionized by molecular docking tools. Still, current molecular docking methods are slow to screen targets, leading to missed candidates and unexpected side effects in clinical trials, despite the potential benefits of this approach. Researchers from the University of Warsaw and others present RAPIDDOCK, an effective transformer-based model for blind molecule docking, to close this gap. With a 100x speed advantage, the molecular docking technique RAPIDDOCK beats current approaches on DockGen benchmarks. It has an average inference time of 0.04 seconds on a single GPU and reaches 52.1% and 44.0% success rates on the Posebusters and DockGen benchmarks, respectively. A personalized loss function, pre-training on protein folding, and relative distance embeddings of 3D structures are important characteristics.

Medicine will be transformed by speeding up the drug discovery process. Since the majority of new medications are small compounds, a number of deep-learning techniques have been put forth to make the process of docking these molecules to druggable protein targets more efficient. None of these techniques are quick and accurate, despite their impressiveness. In reality, a chemical must be screened against thousands of proteins to get a complete picture of its effects. On the other hand, cutting-edge techniques report run times on the order of seconds per protein on a single GPU. It would therefore take years, even with hundreds of GPUs, to scan a tiny database of one million compounds against the proteome, or all of the proteins in the human body. Such timelines are unacceptable in the process of developing new drugs.

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[bichitosdecolores]

hello science comunity of tumblr i need your help.

does anyone know of a free tutorial / youtube series / book or anything like that about molecular docking between ssDNA (specifically, an aptamer) and proteins?

it would be very helpfull if it also includes how to obtain and optimize the tridimentional structure of the DNA molecule

for reference i know pretty much nothing of molecular docking as a whole so anything would be really appreciated

thank you :3

[i-am-q]

[softlabsgroup05]

Unlock the potential of AI in drug discovery and development! Explore the diverse range of AI technologies driving innovation in pharmaceuticals, from virtual screening to molecular modeling. Stay ahead in manufacturing with Softlabs Group, your source for the latest AI insights.

[jppres]

Potential of polyether ionophore compounds as antimalarials through inhibition on Plasmodium falciparum glutathione S-transferase by molecular docking studies

Image: Flickr Article published in J. Pharm. Pharmacogn. Res., vol. 10, no. 6, pp. 1139-1148, November-December 2022. DOI: https://doi.org/10.56499/jppres22.1478_10.6.1139 Alfian Wika Cahyono1,2, Icha Farihah Deniyati Faratisha1, Nabila Erina Erwan1,3, Rivo Yudhinata Brian Nugraha1,4, Ajeng Maharani Putri1,3, Loeki Enggar Fitri1,4* 1Malaria Research Group, Faculty of Medicine, Universitas…

[covid-safer-hotties]

Reference saved in our archive

Covid's constant rapid mutation is driving a continuing pandemic. "Let 'er rip" is costing lives, money, and medicine when common-sense and highly-effective nonpharmaceuticals like masks, air filtration, and ventilation are readily available yet rarely implemented.

Highlights •There were trends of mutations in the S protein of the omicron SARS-CoV-2 variant. •The studied ARVds exhibited adequate solubility, distribution and partition coefficient. •ARVds molecularly interacted with target sites of mutations.

Abstract The multiple mutation of the spike (S) protein of the Omicron SARS-CoV-2 variant is a major concern, as it has been implicated in the severity of COVID-19 and its complications. These mutations have been attributed to COVID-19-infected immune-compromised individuals, with HIV patients being suspected to top the list. The present study investigated the mutation of the S protein of the omicron variant in comparison to the Delta and Wuhan variants. It also investigated the molecular interactions of antiretroviral drugs (ARVd) vis-à-vis dolutegravir, lamivudine, tenofovir-disoproxilfumarate and lenacapavir with the initiation and termination codons of the mRNAs of the mutated proteins of the omicron variant using computational tools. The complete genome sequences of the respective S proteins for omicron (OM066778.1), Delta (OK091006.1) and Wuhan (NC 045512.2) SARS-CoV-2 variants were retrieved from the National Center for Biotechnology Information (NCBI) database. Evolutionary analysis revealed high trends of mutations in the S protein of the omicron SARS-CoV-2 variant compared to the delta and Wuhan variants coupled with 68 % homology. The sequences of the translation initiation sites (TISs), translation termination sites (TTSs), high mutation region-1 (HMR1) and high region mutation-2 (HMR2) mRNAs were retrieved from the full genome of the omicron variant S protein. Molecular docking analysis revealed strong molecular interactions of ARVd with TISs, TTSs, HMR1 and HMR2 of the S protein mRNA. These results indicate mutations in the S protein of the Omicron SARS-CoV-2 variant compared to the Delta and Wuhan variants. These mutation points may present new therapeutic targets for COVID-19.

[everythingaboutbiotech]

Common uses of bioinformatics

💡Sequence analysis Analyzing DNA and protein sequences to identify genes, regulatory regions & mutations.

💡Gene expression Analyzing RNA expression data from experiments like microarrays or RNA-seq to understand gene regulation.

💡Phylogenetics Constructing evolutionary relationships between organisms based on genetic data and genomic comparisons.

💡Molecular modeling Predicting protein structure and docking drugs to proteins using computational modeling and simulation.

💡Databases & Data mining Developing databases like GenBank to store biological data and mining it to find patterns.

💡Genomics Studying entire genomes, including sequencing and assembling genomes as well as identifying genes and genomic variations.

Follow @everythingaboutbiotech for useful posts.

[spyridonya]

i will be an enabler. “ may i have this dance? “ for sophus and raphael could be fun maybe? 👀

oh my god i have an enabler than enabled me to write over 1500 words for the first time in months, thank you romeo! ❤️ first time trying to write in 2nd person, which normally isn't my thing, but we'll just blame the game's narrator.

sacred romantic raph being an ass moments meme

The uncanny stillness of the eternal gloom seeps into flesh and bones, even under the shelter of lacy moonlight. The sensation of coiling vastness would disquiet any soul, yet you find yourself reminded of the antipeak hours of your home when the wane of the luminescence leaves all to lantern light. This is not an unknown concept to the singular tadpole that remains coiled just behind your eye; you are both creatures of the planes on the most molecular level. The lapping sounds of water are still alien to your ears despite its gentleness, it's the strumming of Alfira's lute from far away that puts you at ease, the lazy notes falling like snowflakes upon your nerves, and the bard none the wiser.

The sound of teleportation makes your tadpole jump, though years of training that keeps you from the startle from rolling down your body, and keeping you still as a stone as the notes continue to waver in the air, the commotion too far for Alfira's attention. But that moment of panic is brief, you recognize the sound of this particular user.

It's not that uncommon of a skill, most arcane weavers can attest the sounds of a teleportation spell are based from it's point of origin. You wouldn't know the difference between the sounds of the Elemental Plane of Water from the Heavens, but you know the sounds of the Lower Planes. You won't ever forget the horrific timbre that aches like a soul shredded between rusty gears. 

You knew it long before the cambion set eyes upon you and yours upon him.

You don't give him the satisfaction of turning to him, presenting the solid wall of your back to him, a move that would have your comrades in the Cage mutter as if you had gone addled in the brain-box. An action that would make your current comrades mutter as if you had gone mad. 

The cambion’s steps are slow and purposeful against the ancient wood, making Raphael sound heavier than a man his size should be.

It's an old rage that makes your hand move, and your arms follow as the glaive swings. The weight feels sluggish in your hands, though the powerful muscles of your arms and the twist of your torso carry the motion until the blade just stops at the cambion's throat. Above the blade, Raphael grins, his teeth white against the copper of his skin.

You hate acknowledging how fetching that smile is, as if he were not your elder by millennia in truth and decades by appearance. That coyness is so strange and you find the pulse in your throat is throbbing as if you're the one with blade point against skin.

"Such unfathomable treatment of a guest, my dear boy. One would think you're displeased to see me."

"Whatever made you believe that, princeling?" You grit out; you know he's a cambion but not his sire. But cambions do not become this powerful without some false pride of their mastris on their tongue. You have your notions, but don't speak them.

"Ah, Sophus, you wound me- or have attempted at the least." Raphael chuckles lightly, his hand gently pushing the pole of the glaive from him in a slow arch, and you allow him to do so. Those heavy footsteps creak against the planks of the old dock once more, “You seem most eager to create of me an adversary.” Your gaze is hard as it narrows down upon the human form of the cambion, despite how you lower your weapon.

Raphael stops at his comfortable distance, a sentiment not entirely shared by you as your muscles tense. The cambion does not bring a rhyme to the curl of his lips nor show the flash of his teeth, he merely studies you with that coy gaze of his as darkness shrouds his amber eyes. “What are you here for?” You ask, knowing his old enemy is dead and in the Hells. Suddenly, you remember the child and your hand tightens on your weapon, “Not the girl, not Mol.”

“For all your sharp teeth, little mouse, you forget yourself and your mind. You know as well as me that such investment in a child would never mature so rapidly.” He lifts his arms in a shrug, the motion muscle under the doublet that he wears is noticeable, “Let her grow, let her learn. Isn’t it far safer for her to know the dealings of the law than the grind of the Abyss?” A striking motion of his hand, and his amber gaze meets your steel. “No, no. Do not think that of me. Rather, I came to offer something else.”

You mutely realize that your back is to the water while the cambion’s to the Last LIght Inn. And yet Alfira’s music still floats about you, defying the stillness of the gloom and the tension of your body. Yet, all Raphael does is smile, offering his hand. His fingers look refined, straight, the tendons perfect and nothing like a man approaching his 50th turn of the spire, much less his possible 2500th.  “May I have this dance?”

There’s no humor in the high cheek bones nor his knowing smile, only a curious tilt of his brows. And he holds this pose for a moment, and you think you will out wait him when he realizes what he’s begun. Your mind flickers to Wyll and the rejection on his face as you turn your head from his dance. You rejected a good man, a good person. 

Your arms lift over your head, to return the glaive to it’s strap on your back and carefully you take Raphael’s hand. 

"I dare not ask if you are aware of any Calimshite dance,” Raphael responds and to his credit, he does not leer at the small triumph he’s won, “Such a question would be an insult to us both. However, a Havana based box step may be unfamiliar in name, but perhaps not in motion?"

The cambion's hand is warm in yours, his hand steady on your hip, yours upon his, and blood hammers in your ears as you follow his first step all the while your mind screams to stop.

In no time at all, you are led into a dance as Alfira continues to play to her unknown audience of two. Raphael is right, you may not know the name, but you know the motions and the damnable cambion knows each step - practiced until perfect. 

“In terms of asking a question that would insult either one of us, what are you getting at, Raphael?” You ask quietly, not sure what the tieflings above you in the inn would think of such dance or the intimacy of a cambions warmth not quite against your body. You try not to think of it as well, your mouth straight, your eyes narrow - even if old shames creep into your mind - a moment of wondering if the cambion truly likes what he sees. 

Or what he can harvest from you. 

“A planer-touched greeting to his fellow kin, even if we’re not entirely neighbors.” He replies with that charming grin as he leads you from the length of the dock that stretches over the water and closer to to the shallows that lead up into the Inn. “What is after this grand, heroic gesture of yours? Do you perhaps have a faction in the Cage that would approve of such?” The cambion’s grin stretches, seeing the line on your face, the lowering of your eyes. “I could help you get home… if you wish to go home.”

That is when you stop, that is when you pull away, your heavy steps creaking under you, not trusting the way your body reacts to the question and the way you breathe through your nose. 

Raphael does not look insulted, not ashamed, not even smug with that little curve of his smile. Rather he stands straight and tall, though he barely reaches your chin, and regards you in a way that makes you feel small despite your being far taller and larger. 

You find you want to wipe this expression of his face, hold him down and-

“I do not take silence as a no, little mouse,” The irony of that nickname isn’t lost, “Nor a yes… but an aasimar hiding as a half elf can only keep the ruse for so long, if only to himself. This is not your home, Sophus Firesbane. This place is so alien to your senses and to the powers that call themselves gods offend your sense of fairness.” The cambion takes a step back, then another, and this time you don’t follow, “Perhaps even more than you are offended by me.” And his tone becomes rumbly smoke, “Though I don’t believe you’re as offended by me as you wish you were.”

You don’t strike this time, though your arm aches to move. Once more you glare, “My oath is far more important than your promises.” From all that you’ve learned about fiends, you know how prized a paladin soul truly is to fiendkin. Including cambions with powerful sires never spoken.. 

“That oath of yours,” Raphael shakes his head, the dark mahogany of his hair almost tumbling from its perfect coif. “You’ve a long way in the darkness ahead, little mouse. Perhaps this will be a conversation for another time, if you survive.”  There is a scent of brandy, cherries, and sulfur that sours the sweetness - and the sound of souls being torn by rusty iron gears. “I hope that you do.” 

Once more you find yourself almost alone in the darkness, save for your silent and comfortable tadpole.

[claphandsound]

Out of the question

swim whole schools of questions

flashing in and out

of each other’s shadows

and always followed by a hook

with a point:

Why are there more questions than stars?

How can a small child seeing

through her tiny retina take in

the whole of a starry night sky?

What if our universe is a molecular

speck inside another universe?

Mommy, where do people go when they die?

Do they sometimes get hungry?

What does a whale’s song

sound like to another whale?

What does it sound like to the krill?

How many poets does it take

to change a community?

How many politicians does it take

to change it back?

What shape is love? A sphere?

Does it expand beyond the edges of creation?

Is love what creation is made out of?

How many years of light-speed journeying

brought these glimmer points

to this black mirror of lake

on a dark dot in the Milky Way

where we stand right now

on a softly sighing dock?

© Scott Thompson

[jynersq]

personally i think the field of molecular biology could stand to be a little sexier. we’d get better engagement from the lay population if there was more sucking and fucking. none of this “elucidating the mechanism blah blah blah” shit i want to hear about proteins horny for binding and docking. if we anthropomorphized oncogenic gene fusion products as problematic codependent white men the girls WOULD solve cancer

[cbirt]

Deep learning is being utilized in the course of drug development to understand the structure of the protein-ligand complex, utilizing the technique of virtual structure measurement that combines docking and deep learning despite limitations in accuracy and efficiency. Here, researchers from Nanjing University demonstrate that a single multi-task geometric deep learning model, LigPose, can accurately handle these two basic tasks. LigPose uses graphs to represent ligand and protein combinations to optimize the three-dimensional structure of complexes. It allows for one-step prediction without the need for docking tools by learning atomic interactions and binding strength. LigPose demonstrates state-of-the-art performance in drug discovery, according to extensive studies, suggesting a viable AI-based drug development pipeline.

Small organic molecules (SOM), which make up 72% of FDA-approved medications, are crucial to clinical treatment. Protein-ligand complexes, created when SOM binds to target proteins, show bioactivities and provide direction for the creation of structure-based medicines. Comprehending these complexes at the molecular level facilitates lead optimization and drug screening. Traditional techniques, such as cryo-electron microscopy and X-ray diffraction, need a lot of time and resources.

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[seasmoon]

more details for PIRATE'S LIFE verse:

tsireya was not sirena's killer. it was her spirit-brother, rotxo. because of their empathic-psychic link, she took his place as captive of the fishmonger family, paying for his crime. as their people's shaman and the daughter of their spiritual leader, she took it upon herself to protect him. the metkayina harbor a strong sense of communal accountability; it was only natural that one of their strongest fae take on the burden.

she was aided in escaping by the youngest of the family's seven brothers. he was bullied by his older siblings throughout his childhood, and tsireya treated him as a genuine spirit-sibling, so there was a morbid sense of camaraderie between them. both, in a way, felt like captives. he helped her steal a horse from the stables and she quickly rode it out of the estate, and towards the nearest town.

sirena is actively searching for safe passage to the nearest shipping dock or beach. she has the hunter's spirit to protect her, and the calls from their deathless ancestors across the great ocean.

time moves differently in the spirit realm (oceans, skies, etc.). by all accounts, sirena's soul has spent decades there, and simultaneously with landlocked tsireya. she is considered a part of the metkayina's spiritual family. adopted. sirena spent too much of her life with the water, and she felt spiritually estranged with her "biological" family, who were psychologically and ideologically colonial.

mercenaries, marines, and occultists pursue them. but tsireya is a powerful water spirit, and all water spirits experience a form of cledomancy. she foresees danger and acts accordingly, but the warnings are not always linear or clear, relied on "instinct" and "superstition." she uses her siren's voice if necessary, as well. additionally, hunters drown their victims by using bioluminescent hypnosis to completely paralyze their prey in the water or (temporarily) on land for quick escapes.

the metkayina clan possess strong mana. as a tsakarem, tsireya has a powerful relationship with mana.

for oceana/pasifika cultures, "mana" is a word that exists in micronesian, melanesian and polynesian languages that refers to: "supernatural power associated with creativity and excellence. it is inherent in highly respected people (chiefs, leaders, shamans), in sacred objects, and in spiritual forces." (Majorie, Pacific Islands Monthly, circa 1973) because sirena had similar mana, it was instinctual to accept her as a fellow water spirit. in this way, she is "part fish" or "half-fish". but it would be more accurate to say that she is "half-ocean".

through sirena, tsireya and the hunter learn to love the "land". they wish to protect it. some members of the metkayina do not share the same sentiments, and the wrath of spiritual forces can be nightmarish.

tsireya's true, "physical" form is not much different from her look as a na'vi, except with significantly more bioluminescent dermal patterns. when she closes her eyes in the dark, her eyelids appear to be glowing like ghostly pupils (a defensive measure). because water spirits have the molecular structure of liquid ("unstable" atoms, fluidly changing at a molecular level via quantum mechanics), she can still retain sirena's "human" form.

she finds an ally in a jungle-dwelling spirit and trickster demigod, known as lo'ak. half-human, he knows the ways of land-dwelling people, and helps her to understand and navigate a brand new world (to her).

[bichitosdecolores]

i’ve done it!!!

[truebluewhocanoe]

The True Blue You- Author Commentary

Author Notes

Hi! This is the extended Author’s Notes for my fic “The True Blue You”, which you should definitely read BEFORE reading this post.

I like the Dr Nyarlathotep niche of Doctor Who fandom a lot. I want more Dr Nyarlathotep content (that isn’t porn). I figured a good way to promote that would be to write out my own thoughts on one of my Dr Nyarlathotep works and talk about how it came together. This is that! Most of this is going to be me talking about particular passages from the fic, the thought that went into them, and the references to other stuff that I’ve snuck in. ✨Let’s begin✨

Commentary

Hence his search for the Zero Room. Wherever he left it. So that he can unravel the extradimensional parts of himself into three-dimensional space and check that everything is in order.

Finding a good word for the Doctor letting out all their Nyarly was hard but I eventually settled on “unravel” and “unfurl”, mainly for the fabric & knitting connotations, because Looms. Aw yeah.

First comes the extraspatial limbs, then the temporal ones. His temporal tendrils and hooks hang in the air around him; vestigial eyes, the crystallised irises of his past bodies, dot his face. He snags a hook on one of his sleeves; he can taste its timeline, senses tracing the thread’s creation and transformation into a garment, tears and stains and cleanings. He deftly unhooks it, then takes a closer look at the sleeve with his fifth set of eyes. Microwave reflections let him peek into the molecular structure. 

First things first: this fic is, as is probably quite obvious to anyone familiar with the Dr Nyarlathotep tag, inspired by “In The Holding Tank I Built For Myself”, which I consider to be more or less the definitive work of this fandom niche. One of the many things I took from Holding Tank and incorporated into my own Dr Nyarlathotep headcanons is the idea that bits of the Doctor’s old bodies get repurposed into their extradimensional body. One of the lines of Holding Tank that stuck out to me the most was the Fifth Doctor’s eyes looking back up at the Doctor- which ends up being pivotal to this fic.

Second: I never actually explain how the Doctor’s clothes adjust to him going Nyarly. I’m not going to explain here, either.

He stretches his wings one set at a time, starting with the small, webbed ones at the base of his primary spine all the way up to the feathered vortex-gliders that span the width of the room when fully outstretched. (And, it should be noted, the Zero Room is much larger than it appears.)

This was inspired by a very old tumblr post (which I can’t find now!!!) headcanoning Time Lords are being, essentially, Time Vortex dragons. The implication is that Time Lords can, in fact, fly around in the vortex under their own power, but use TARDISes to do so the same way we use ships to cross the ocean instead of swimming it. I love this concept and had to weave it in to my personal Nyarly canon.

His hair unspools from short blond curls into nigh-Samsonian locks, closer to fibre-optic cables than keratin follicles. A crown of hard-photon horns sorts the strands, with ivory halos at regular intervals down the length to keep the bundles from separating. He leaves the ends in mind-space where they loop around the TARDIS's psychic docks. He runs his aft right hands through the hairs, untangling knots with crystal-jointed fingers.

I want to say that the Doctor getting extra long glowy anime hair was inspired by Sixie going super saiyan in the PDA The Quantum Archangel and the relevant trope from Dragonball Z, but this section was written within a couple days of the trailer for Xenoblade Chronicles 3 - Future Redeemed coming out, in which another favorite blond character of mine is revealed to have grown out his hair really long, so that’s probably where I actually got the idea from.

Time Lords plugging their hair into their TARDISes to communicate psychically was probably subconsciously inspired by Avatar (the blue people one, not The Last Airbender.)

“Crystal joints” is a phrase I use in another Dr Nyarlathotep fic of mine, A Black Fire Burning, which you could definitely say was the prototype for this fic.

Yes, the Doctor has both halos and horns, and yes, they are used for cable management. Deal with it.

Letting all of himself out is like taking off a corset after a long night.

I’ll let you decide which Doctor out of the First through Fifth has worn a corset. (My money’s on Three.)

She can’t sleep.

You might find some parallels between this fic and my last Who fic, After the Archangel, which also consists of a companion hashing things out with a Doctor after being unable to sleep due to a traumatizing adventure. I guess I have a type.

Which leads her back to the elephant in the room. The Doctor wasn’t like this when she first met her. The Doctor she’d met had been open and amiable and polite. And then he died and left her with someone she didn’t understand. Someone who apparently was not alright in the head after having come back to life, who is supposedly fine now but not the same as the way he was before.

And so we reach the elephant in the room that is this fic: I do not like that Big Finish tried to squeeze in more adventures with the Fifth Doctor and Peri between Planet of Fire and Caves of Androzani. It ruins all the appeal of their dynamic (not to mention the latter episode, one of the most beloved in all of Classic Who) and just isn’t necessary. So yeah, those episodes are not canon to this fic, and in fact you could say that the conflict of this story is in protest of their existence.

This fic hinges on the fact that Peri still would’ve had a bumpy go of things with the Fifth Doctor, because he also wasn’t a very pleasant guy to most of his companions (no shade, that’s just how 80s Who went), and also ran into a ton of extremely horrible situations! Peri’s successful companionship with the Doctor comes in spite of those facts. 

Writing the dynamic (and specifically, power dynamic) between Peri and the Doctor is a very tricky wire to walk but I think I did okay, in the end. The Sixth Doctor and Peri boxset by Big Finish ends on a note of the Doctor and Peri accepting that their life together probably isn’t very sane or healthy, but they do it anyways because they enjoy it. That’s the perspective I was trying to convey here. But that’s jumping the gun a little- let’s go back to the fic.

She looks at it, a great big thorny mass, as if M.C. Escher had knitted a scarf out of barbed wire. Then, without her even blinking, the thing bends, changing without changing, the duck’s head into a rabbit’s, and she sees a great spider’s web, or perhaps anemone, a thing of tendrils and gravity-defying lines. 

The ‘thorny mass’ is inspired by a certain alien structure in the book Blindsight by Peter Watts. I finished reading it right around when I started writing this fic and really wanted to sneak in something from it, mainly because it’s a great sci-fi horror book (as much as describing it as such is an injustice to all it is.) The “duck’s head into a rabbit’s” is a reference to the duck-rabbit illusion, which is also utilized in Blindsight. (Seriously, even referencing that book in my own work is a grave act of authorial hubris. I am not worthy!)

Then, something catches her attention, a blip on the radar of her millennia-made pattern-matching instincts, a slap of color and pattern that can’t be right, must be a trick of the light, a name in the static, Virgin Mary in the burnt toast. 

Invoking pareidolia here.

like the figurehead on the bow of a great ship

This was one of the central mental images I had going into this fic.

Humans consider the smooth eversion of a sphere, the simplest three-dimensional object, to be a form of paradox

“Smooth eversion of a sphere” means turning it inside out without breaking the rules of topology, as you might have seen explained in this perennially recommended YouTube video.

but his larboard greater forewing

Larboard is an outdated nautical term for “the left of the ship”, which was replaced by “port” due to how similar to “starboard” is sounded. Including it here is a reference to its infamous use in a certain fight in Final Fantasy XIV. I knew I wanted to use “larboard” to describe something of the Doctor’s Nyarlyness, which inspired the use of the similarly nautical “aft” earlier in the fic.

From seemingly random places across his body, purple-gold strands of what looks like stardust reach outwards, pulled taut clinging to thin air.

Inspired by, of all things, Origin Forme Giratina, as elucidated in this tumblr post.

She can’t make out his legs, the lower half of his body caught in a mirage with the posture of Schrodinger’s indecisive cat.

Of course, my headcanon for Sixie’s Nyarlathotep form is a bit more than “eldritch cat”, but I still wanted to work something feline in. The Doctor’s form seeming to be multiple things at once in a quantum sort of way was inspired by they'll turn me in your arms, lady by @lurking-latinist.

She can make out his face. It's almost the same, save for the spots that shine like jewels dotting it in two parallel lines like tear-trails beneath his eyes.

Knowing that the topmost pair of "jewels" is the Fifth Doctor's eyes, the mentioned “dozen" implies that every regeneration adds another pair, bumping the rest further down. A Time Lord on their last regeneration probably has eyes down to their collarbones!

Hold on, his arm shouldn't be bending that far. Counts the fingers on each hand- six. Wait, that’s not right.

I originally planned a bit where the Doctor held up all his fingers when checking that Peri was OK, only for her to count more than ten of them, but it didn't really work logistically (moved the Doctor checking Peri from the hallway to her room) or tonally (not the right place for humor.)

aquamarine nodules

I solemnly vow to never refer to the Fifth Doctor's eyes as "aquamarine nodules" ever again.

Hey, at least I didn’t call them "orbs"

“Um, Zee- Zed, sorry, Y, X, W, U, no, I mean V, then U, T, S, Q- is it Q?”

[...]

“Um, I was a kid playing in the backyard and a ladybug landed on my hand,” she manages to spit out, “And my mom told me about how they’re helpful because they eat other bugs.”

The Doctor sticks out an index finger, pointing up. “Follow my finger with your eyes and tell me more about ladybirds.”

“Lady- oh, right.

Emphasizing the emotional distance between two characters by highlighting their linguistic differences.

She couldn't quite make out what it was he was expecting her to say, so instead she looks a bit higher, at the strangely familiar blue… things… on his face.

Can you tell that I REALLY didn't want to call them orbs?

"I'm afraid I can't answer that, Peri," he responds, and she expects him to leave it at that but he continues, "Wanderlust is a powerful thing, not to mention its cousin, curiosity. I can only speak from my own experiences, but I find the more painful parts of the universe to spur me further onwards. Both to find the brighter spots, and to help where I can."

[...]

"In all my experience with your kind, Peri, I've found that no one is ever 'just' something. You're much, much more than that, Perpugilliam Brown."

Writing TV!Sixth Doctor is hard. Really hard. It’s hard to pull something consistent out of a character that was being actively sabotaged by the writers. So if it seems like EU!Sixth Doctor just shows up out of nowhere once we switch to Peri’s last POV section: sorry! I tried my best to communicate how unsure the Doctor is of where he takes this conversation. He’s more or less defaulting to mirroring what Peri throws at him… right when she takes a leap of faith and opens up to him. This is, more or less, supposed to be the moment in Sixie’s life where he realizes the value of not being so damn prickly all the time. He comes out of this story kind, if not quite wise to human nature yet. He’ll get there!

He pauses, and reaches up to feel his face. Back to normal. 

An idea occurred to me to imply that some remnant of the Fifth Doctor kept the eyes out in a really weird self-wingman tactic, but I don't like the implication that the past incarnations are separate consciousnesses, so I didn't go through with it

It's at that moment the Doctor realizes that Peri is, for all intents and purposes, more accepting of his being a polydimensional monstrosity with vestigial bits of his own corpses repurposed as sensory organs, than she is of his fashion sense.

“Monstrous” being the word that the Doctor mouthed earlier to complete Peri’s sentence. The biggest difference between this fic and the aforementioned Holding Tank is that the Sixth Doctor lacks the self-hatred the Doctor has regarding his Nyarlyness in that fic (and that the Fifth Doctor is implied to have in this one.) That’s TV!Six’s pride coming in to play. But as we see after Peri sees him, he’s got some frustrations with the fact that his full existence is inherently dangerous to other species. At some point during his conversation with Peri, it does occur to him that she very easily could have left the TARDIS over this, hence his final words to her before bidding her goodnight.

Closing Thoughts

Overall, my goals for this fic were: 1. Believably write the Doctor and Peri coming to an understanding after Season 22 that doesn’t just full-on retcon the shitty writing (yes, a lot of their interactions that season are just poorly written.) and 2. Write a long Dr Nyarlathotep fic that doesn’t resort to just making the Sixth Doctor an eldritch cat AND doesn’t use the word “tentacle” at any point, because that’s not what I’m about. I personally think I met both those goals, so I’m quite proud! Hopefully it produced a fun read. And thank you for reading this full-on author commentary!

[romancestual]

"Aria Above Seattle" from Arias by Sharon Olds.

Transcript:

About to land—in the state which used to be islands, till the ocean floor dove under the continent, bringing the masses of rock in, to dock—I remember that my father is buried here. Not his hair, twenty years long in the grave, not his body, distilled by the soil’s rotgut, but his ashes—for the first time in years I am near my father’s bones, ground and rendered, and I want to go in, where they are, and play among their ochre spheres, as if I could be in a stone tumbler with him, or soar, fellow solar orbiter, inside an atom of his, neutrons and protons and electrons of his ungainsayable existence—there can never be a world, here, whatever happens, in which my father will have not existed. I want to say I loved my father, always, on the molecular level—I love the word love, I want to wear it as the human clothing, though I know I do not know what it means for someone to love, to honor, their father and mother. Well, I will hold to the geological record, here is where the mantle bent, here is where the magma came up through the mile of glacier. And I feel that if I could hold some of those tiny, round dice of his calcium and marrow I might be feeling what any girl on a playground would feel with her beloved marbles. I know— wanting the animal evidence in my palm, as if to own, to dote, spiritless, on matter…but I have my hopes of what could come, for me, from knowing there are forms of love unknowable to me.