Elucidating molecular mechanisms of functional conformational changes of proteins via Markov state models.
Sign Up to like & getrecommendations! Published in 2020 at "Current opinion in structural biology"
DOI: 10.1016/j.sbi.2020.10.005
Abstract: Functional conformational changes of proteins can facilitate numerous biological events in cells. The Markov state model (MSM) built from molecular dynamics simulations provide a powerful approach to study them. We here introduce a protocol that… read more here.
Keywords: mechanisms functional; markov state; functional conformational; changes proteins ... See more keywords
Impact of Nonnative Interactions on the Binding Kinetics of Intrinsically Disordered p53 with MDM2: Insights from All-Atom Simulation and Markov State Model Analysis
Sign Up to like & getrecommendations! Published in 2024 at "Journal of chemical information and modeling"
DOI: 10.1021/acs.jcim.3c01833
Abstract: Intrinsically disordered proteins (IDPs) lack a well-defined tertiary structure but are essential players in various biological processes. Their ability to undergo a disorder-to-order transition upon binding to their partners, known as the folding-upon-binding process, is… read more here.
Keywords: intrinsically disordered; simulation markov; nonnative interactions; p53 ... See more keywords
Mapping Conformational and Kinetic Landscapes of 14-3-3σ/α-Synuclein Assembly via Variational Autoencoders and Markov State Models.
Sign Up to like & getrecommendations! Published in 2025 at "Journal of chemical information and modeling"
DOI: 10.1021/acs.jcim.5c02323
Abstract: The interaction between the molecular chaperone 14-3-3σ and the intrinsically disordered protein α-synuclein is implicated in the pathogenesis of Parkinson's disease, yet its dynamic mechanism remains poorly understood at an atomistic level. The inherent flexibility… read more here.
Keywords: synuclein assembly; mapping conformational; variational autoencoders; state models ... See more keywords
Structural Features and Energetics of the Periplasmic Entrance Opening of the Outer Membrane Channel TolC Revealed by Molecular Dynamics Simulation and Markov State Model Analysis
Sign Up to like & getrecommendations! Published in 2019 at "Journal of chemical information and modeling"
DOI: 10.1021/acs.jcim.8b00957
Abstract: TolC is a channel protein responsible for substrate translocation across the outer membrane, and it is also a part of the tripartite multidrug efflux pumps in Gram-negative bacteria. The crystal structure of TolC shows that… read more here.
Keywords: markov state; periplasmic entrance; outer membrane; tolc ... See more keywords
Markov State Model Analysis of Haloperidol Binding to the D3 Dopamine Receptor.
Sign Up to like & getrecommendations! Published in 2020 at "Journal of chemical theory and computation"
DOI: 10.1021/acs.jctc.0c00013
Abstract: We have developed Markov state models (MSMs) and hidden Markov models (HMMs) that describe the binding of haloperidol to the D3 dopamine receptor. Haloperidol is an antipsychotic drug that binds with nanomolar affinity to the… read more here.
Keywords: dopamine receptor; methodology; receptor; markov state ... See more keywords
PopShift: A Thermodynamically Sound Approach to Estimate Binding Free Energies by Accounting for Ligand-Induced Population Shifts from a Ligand-Free Markov State Model
Sign Up to like & getrecommendations! Published in 2024 at "Journal of Chemical Theory and Computation"
DOI: 10.1021/acs.jctc.3c00870
Abstract: Obtaining accurate binding free energies from in silico screens has been a long-standing goal for the computational chemistry community. However, accuracy and computational cost are at odds with one another, limiting the utility of methods… read more here.
Keywords: binding free; free energies; popshift; ligand ... See more keywords
Markov State Models Reveal How Folding Kinetics Influence Absorption Spectra of Foldamers.
Sign Up to like & getrecommendations! Published in 2024 at "Journal of chemical theory and computation"
DOI: 10.1021/acs.jctc.4c00202
Abstract: Self-assembly of platinum(II) complex foldamers is an essential approach to fabricate advanced luminescent materials. However, a comprehensive understanding of folding kinetics and their absorption spectra remains elusive. By constructing Markov state models (MSMs) from large-scale… read more here.
Keywords: folding kinetics; absorption spectra; spectra; state models ... See more keywords
Capturing the Effects of Single Atom Substitutions on the Inhibition Efficiency of Glycogen Synthase Kinase-3β Inhibitors via Markov State Modeling and Experiments.
Sign Up to like & getrecommendations! Published in 2024 at "Journal of chemical theory and computation"
DOI: 10.1021/acs.jctc.4c00311
Abstract: Small modifications in the chemical structure of ligands are known to dramatically change their ability to inhibit the activity of a protein. Unraveling the mechanisms that govern these dramatic changes requires scrutinizing the dynamics of… read more here.
Keywords: inhibition; kinase; markov state; glycogen synthase ... See more keywords
Structural Heterogeneity of Intermediate States Facilitates CRIPT Peptide Binding to the PDZ3 Domain: Insights from Molecular Dynamics and Markov State Model Analysis.
Sign Up to like & getrecommendations! Published in 2025 at "Journal of chemical theory and computation"
DOI: 10.1021/acs.jctc.4c01308
Abstract: Intrinsically disordered proteins (IDPs), characterized by a lack of defined tertiary structure, are ubiquitous and indispensable components of cellular machinery. These proteins participate in a diverse array of biological processes, often undergoing conformational transitions upon… read more here.
Keywords: cript peptide; structural heterogeneity; state model; model analysis ... See more keywords
Hierarchical Markov State Model Building to Describe Molecular Processes.
Sign Up to like & getrecommendations! Published in 2020 at "Journal of chemical theory and computation"
DOI: 10.1021/acs.jctc.9b00955
Abstract: Markov state models can describe ensembles of pathways via kinetic networks but are difficult to create when large free energy barriers limit unbiased sampling. Chain-of-states simulations allow sampling over large free energy barriers but are… read more here.
Keywords: large free; markov state; markov; state model ... See more keywords
Prediction of New Stabilizing Mutations Based on Mechanistic Insights from Markov State Models
Sign Up to like & getrecommendations! Published in 2017 at "ACS Central Science"
DOI: 10.1021/acscentsci.7b00465
Abstract: Protein stabilization is fundamental to enzyme function and evolution, yet understanding the determinants of a protein’s stability remains a challenge. This is largely due to a shortage of atomically detailed models for the ensemble of… read more here.
Keywords: prediction new; new stabilizing; stabilizing mutations; markov state ... See more keywords