Balanced Three-Point Water Model OPC3-B for Intrinsically Disordered and Ordered Proteins

Intrinsically disordered proteins (IDPs) play a criticalrole inmany biological processes. Due to the inherent structural flexibilityof IDPs, experimental methods present significant challenges for samplingtheir conformational information at the atomic level. Therefore, moleculardynamics (MD) simulations have emerged as the primary tools for modelingIDPs whose accuracy depend on force field and water model. To enhancethe accuracy of physical modeling of IDPs, several force fields havebeen developed. However, current water models lack precision and underestimatethe interaction between water molecules and proteins. Here, we usedMonte-Carlo re-weighting method to re-parameterize a three-point watermodel based on OPC3 for IDPs (named OPC3-B). We benchmarked the performanceof OPC3-B compared with nine different water models for 10 IDPs andthree ordered proteins. The results indicate that the performanceof OPC3-B is better than other water models for both IDPs and orderedproteins. At the same time, OPC3-B possess the power of transferabilitywith other force field to simulate IDPs. This newly developed watermodel can be used to insight into the research of sequence-disordered-functionparadigm for IDPs.

Automated summary

Intrinsically disordered proteins (IDPs) play critical roles in biological processes, but sampling their conformational information is challenging. Molecular dynamics (MD) simulations have become the primary tool, but the accuracy depends on force field and water model. A new three-point water model named OPC3-B has been developed for IDPs, which outperforms other water models in terms of accuracy and transferability. This water model can provide insights into the research of sequence-disordered-function paradigm for IDPs.