Tutorial on how to build non-Markovian dynamic models from molecular dynamics simulations for studying protein conformational changes.
J Chem Phys
; 160(12)2024 Mar 28.
Article
em En
| MEDLINE
| ID: mdl-38516972
ABSTRACT
Protein conformational changes play crucial roles in their biological functions. In recent years, the Markov State Model (MSM) constructed from extensive Molecular Dynamics (MD) simulations has emerged as a powerful tool for modeling complex protein conformational changes. In MSMs, dynamics are modeled as a sequence of Markovian transitions among metastable conformational states at discrete time intervals (called lag time). A major challenge for MSMs is that the lag time must be long enough to allow transitions among states to become memoryless (or Markovian). However, this lag time is constrained by the length of individual MD simulations available to track these transitions. To address this challenge, we have recently developed Generalized Master Equation (GME)-based approaches, encoding non-Markovian dynamics using a time-dependent memory kernel. In this Tutorial, we introduce the theory behind two recently developed GME-based non-Markovian dynamic models the quasi-Markov State Model (qMSM) and the Integrative Generalized Master Equation (IGME). We subsequently outline the procedures for constructing these models and provide a step-by-step tutorial on applying qMSM and IGME to study two peptide systems alanine dipeptide and villin headpiece. This Tutorial is available at https//github.com/xuhuihuang/GME_tutorials. The protocols detailed in this Tutorial aim to be accessible for non-experts interested in studying the biomolecular dynamics using these non-Markovian dynamic models.
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1
Coleções:
01-internacional
Base de dados:
MEDLINE
Contexto em Saúde:
1_ASSA2030
Problema de saúde:
1_financiamento_saude
Assunto principal:
Proteínas
/
Simulação de Dinâmica Molecular
Idioma:
En
Revista:
J Chem Phys
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
Estados Unidos