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
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
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
Insights into Rational Design of a New Class of Allosteric Effectors with Molecular Dynamics Markov State Models and Network Theory
Sign Up to like & getrecommendations! Published in 2022 at "ACS Omega"
DOI: 10.1021/acsomega.1c05624
Abstract: The development of drugs to restore protein function has been a major advance facilitated by molecular medicine. Allosteric regulation, a phenomenon widely observed in nature, in which a molecule binds to control a distance active… read more here.
Keywords: state models; molecular dynamics; network theory; markov state ... See more keywords
Memory Unlocks the Future of Biomolecular Dynamics: Transformative Tools to Uncover Physical Insights Accurately and Efficiently.
Sign Up to like & getrecommendations! Published in 2023 at "Journal of the American Chemical Society"
DOI: 10.1021/jacs.3c01095
Abstract: Conformational changes underpin function and encode complex biomolecular mechanisms. Gaining atomic-level detail of how such changes occur has the potential to reveal these mechanisms and is of critical importance in identifying drug targets, facilitating rational… read more here.
Keywords: memory unlocks; unlocks future; biomolecular; memory ... See more keywords
Markov state modelling reveals heterogeneous drug-inhibition mechanism of Calmodulin
Sign Up to like & getrecommendations! Published in 2022 at "PLoS Computational Biology"
DOI: 10.1371/journal.pcbi.1010583
Abstract: Calmodulin (CaM) is a calcium sensor which binds and regulates a wide range of target-proteins. This implicitly enables the concentration of calcium to influence many downstream physiological responses, including muscle contraction, learning and depression. The… read more here.
Keywords: calcium; tfp; cam; drug ... See more keywords
Diffusion of molecules through nanopores under confinement: Time-scale bridging and crowding effects via Markov state model
Sign Up to like & getrecommendations! Published in 2022 at "Biomolecular Concepts"
DOI: 10.1515/bmc-2022-0019
Abstract: Abstract Passive transport of molecules through nanopores is characterized by the interaction of molecules with pore internal walls and by a general crowding effect due to the constricted size of the nanopore itself, which limits… read more here.
Keywords: molecules nanopores; transport; state model; crowding effects ... See more keywords