Development of Charge-Augmented Three-Point Water Model (CAIPi3P) for Accurate Simulations of Intrinsically Disordered Proteins
| Autor: | João V de Souza, Francesc Sabanés Zariquiey, Agnieszka K. Bronowska |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
Models
Molecular 0301 basic medicine Protein Conformation Molecular Dynamics Simulation Intrinsically disordered proteins 01 natural sciences Article Catalysis Force field (chemistry) Inorganic Chemistry lcsh:Chemistry 03 medical and health sciences Partial charge Molecular dynamics Molecular recognition X-Ray Diffraction Scattering Small Angle 0103 physical sciences Water model Physical and Theoretical Chemistry Molecular Biology lcsh:QH301-705.5 Spectroscopy Physics 010304 chemical physics Organic Chemistry Solvation Water General Medicine molecular dynamics Computer Science Applications water models CAIPi3P 030104 developmental biology IDPs lcsh:Biology (General) lcsh:QD1-999 Solvent models Chemical physics Solvents intrinsically disordered proteins |
| Zdroj: | International Journal of Molecular Sciences, Vol 21, Iss 6166, p 6166 (2020) International Journal of Molecular Sciences Volume 21 Issue 17 |
| DOI: | 10.26434/chemrxiv.7706867.v1 |
| Popis: | Intrinsically disordered proteins (IDPs) are molecules without a fixed tertiary structure, exerting crucial roles in cellular signalling, growth and molecular recognition events. Due to their high plasticity, IDPs are very challenging in experimental and computational structural studies. To provide detailed atomic insight in IDPs&rsquo dynamics governing their functional mechanisms, all-atom molecular dynamics (MD) simulations are widely employed. However, the current generalist force fields and solvent models are unable to generate satisfactory ensembles for IDPs when compared to existing experimental data. In this work, we present a new solvation model, denoted as the Charge-Augmented Three-Point Water Model for Intrinsically Disordered Proteins (CAIPi3P). CAIPi3P has been generated by performing a systematic scan of atomic partial charges assigned to the widely popular molecular scaffold of the three-point TIP3P water model. We found that explicit solvent MD simulations employing CAIPi3P solvation considerably improved the small-angle X-ray scattering (SAXS) scattering profiles for three different IDPs. Not surprisingly, this improvement was further enhanced by using CAIPi3P water in combination with the protein force field parametrized for IDPs. We also demonstrated the applicability of CAIPi3P to molecular systems containing structured as well as intrinsically disordered regions/domains. Our results highlight the crucial importance of solvent effects for generating molecular ensembles of IDPs which reproduce the experimental data available. Hence, we conclude that our newly developed CAIPi3P solvation model is a valuable tool for molecular simulations of intrinsically disordered proteins and assessing their molecular dynamics. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|