46 hasil untuk "Ferguson, Andrew L."
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Artikel Jurnal Teks lengkap
Molecular latent space simulators
Small integration time steps limit molecular dynamics (MD) simulations to millisecond time scales. Markov state models (MSMs) and equation-free approaches learn low-dimensional kinetic models from MD simulation data by performing configurational or dynamical coarse-graining of the state space. The…
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Data-driven prediction of α(IIb)β(3) integrin activation paths using manifold learning and deep generative modeling
The integrin heterodimer is a transmembrane protein critical for driving cellular process and is a therapeutic target in the treatment of multiple diseases linked to its malfunction. Activation of integrin involves conformational transitions between bent and extended states. Some of the…
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Free energy calculations of the functional selectivity of 5-HT(2B) G protein-coupled receptor
G Protein-Coupled Receptors (GPCRs) mediate intracellular signaling in response to extracellular ligand binding and are the target of one-third of approved drugs. Ligand binding modulates the GPCR molecular free energy landscape by preferentially stabilizing active or inactive conformations that…
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Learning the relationship between nanoscale chemical patterning and hydrophobicity
The hydrophobicity of proteins and similar surfaces, which display chemical heterogeneity at the nanoscale, drives countless aqueous interactions and assemblies. However, predicting how surface chemical patterning influences hydrophobicity remains a challenge. Here, we address this challenge by…
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ProtWave-VAE: Integrating Autoregressive Sampling with Latent-Based Inference for Data-Driven Protein Design
Deep generative models (DGMs) have shown great success in the understanding and data-driven design of proteins. Variational autoencoders (VAEs) are a popular DGM approach that can learn the correlated patterns of amino acid mutations within a multiple sequence alignment (MSA) of protein sequences…
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Artikel Jurnal Teks lengkap
Machine learning-enabled discovery and design of membrane-active peptides
Antimicrobial peptides are a class of membrane-active peptides that form a critical component of innate host immunity and possess a diversity of sequence and structure. Machine learning approaches have been profitably employed to efficiently screen sequence space and guide experiment towards…
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Determining Sequence-Dependent DNA Oligonucleotide Hybridization and Dehybridization Mechanisms Using Coarse-Grained Molecular Simulation, Markov State Models, and Infrared Spectroscopy
[Image: see text] A robust understanding of the sequence-dependent thermodynamics of DNA hybridization has enabled rapid advances in DNA nanotechnology. A fundamental understanding of the sequence-dependent kinetics and mechanisms of hybridization and dehybridization remains comparatively…
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Disruption of energetic and dynamic base pairing cooperativity in DNA duplexes by an abasic site
DNA duplex stability arises from cooperative interactions between multiple adjacent nucleotides that favor base pairing and stacking when formed as a continuous stretch rather than individually. Lesions and nucleobase modifications alter this stability in complex manners that remain challenging to…
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Tetranucleosome Interactions Drive Chromatin Folding
[Image: see text] The multiscale organizational structure of chromatin in eukaryotic cells is instrumental to DNA transcription, replication, and repair. At mesoscopic length scales, nucleosomes pack in a manner that serves to regulate gene expression through condensation and expansion of the…
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Prediction of [Formula: see text] integrin structures along its minimum free energy activation pathway
The adhesion protein integrin is a transmembrane heterodimer that plays a pivotal role in cellular processes such as cell signaling and cell migration. To execute its function, integrin undergoes extensive conformational changes from a bent-closed to an extended-open state. Resolving the structures…
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Systematic determination of order parameters for chain dynamics using diffusion maps
We employ the diffusion map approach as a nonlinear dimensionality reduction technique to extract a dynamically relevant, low-dimensional description of n-alkane chains in the ideal-gas phase and in aqueous solution. In the case of C(8) we find the dynamics to be governed by torsional motions. For…
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Machine learning antimicrobial peptide sequences: Some surprising variations on the theme of amphiphilic assembly
Antimicrobial peptides (AMPs) collectively constitute a key component of the host innate immune system. They span a diverse space of sequences and can be α-helical, β-sheet, or unfolded in structure. Despite a wealth of knowledge about them from decades of experiments, it remains difficult to…
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Mapping membrane activity in undiscovered peptide sequence space using machine learning
There are some ∼1,100 known antimicrobial peptides (AMPs), which permeabilize microbial membranes but have diverse sequences. Here, we develop a support vector machine (SVM)-based classifier to investigate ⍺-helical AMPs and the interrelated nature of their functional commonality and sequence…
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Natural Language Prompts Guide the Design of Novel Functional Protein Sequences
The advent of natural language interaction with machines has ushered in new innovations in text-guided generation of images, audio, video, and more. In this arena, we introduce Bio logical M ulti- M odal M odel ( BioM3 ), as a novel framework for designing functional proteins via natural language…
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Data-driven discovery of cardiolipin-selective small molecules by computational active learning
Subtle variations in the lipid composition of mitochondrial membranes can have a profound impact on mitochondrial function. The inner mitochondrial membrane contains the phospholipid cardiolipin, which has been demonstrated to act as a biomarker for a number of diverse pathologies. Small molecule…
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Molecular insight into how the position of an abasic site modifies DNA duplex stability and dynamics
Local perturbations to DNA base-pairing stability from lesions and chemical modifications can alter the stability and dynamics of an entire oligonucleotide. End effects may cause the position of a disruption within a short duplex to influence duplex stability and structural dynamics, yet this…
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Artikel Jurnal Teks lengkap
Molecular insight into how the position of an abasic site and its sequence environment influence DNA duplex stability and dynamics
Local perturbations to DNA base-pairing stability from lesions and chemical modifications can alter the stability and dynamics of an entire oligonucleotide. End effects may cause the position of a disruption within a short duplex to influence duplex stability and structural dynamics, yet this…
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Artikel Jurnal Teks lengkap
Translating HIV sequences into quantitative fitness landscapes predicts viral vulnerabilities for rational immunogen design
A prophylactic or therapeutic vaccine offers the best hope to curb the HIV-AIDS epidemic gripping sub-Saharan Africa, but remains elusive. A major challenge is the extreme viral sequence variability among strains. Systematic means to guide immunogen design for highly variable pathogens like HIV are…
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An Experimental and Computational Investigation of Spontaneous Lasso Formation in Microcin J25
The antimicrobial peptide microcin J25 (MccJ25) is posttranslationally matured from a linear preprotein into its native lasso conformation by two enzymes. One of these enzymes cleaves the preprotein and the second enzyme installs the requisite isopeptide bond to establish the lasso structure…