{"title":"Methodological and force field effects in the molecular dynamics-based prediction of binding free energies of host–guest systems","authors":"Zhaoxi Sun and Piero Procacci","doi":"10.1039/D4CP01804D","DOIUrl":null,"url":null,"abstract":"<p >As a contribution to the understanding and rationalization of methodological and modeling effects in recent host–guest SAMPL challenges, using an alchemical molecular dynamics technique we have examined the impact of force field parameterization and ionic strength in connection with guest charge neutralization on computed dissociation free energies in two typical SAMPL heavily charged macrocyclic hosts encapsulating small protonated amines with disparate binding affinities. We have shown that the methodological treatment for host neutralization, with explicit ions or with the background neutralizing plasma in the context of alchemical calculations under periodic boundary conditions, has a moderate effect on the calculated affinities. On the other hand, we have shown that seemingly small differences in the force field parameterization in highly symmetric hosts can produce systematic effects on the structural features that can have a significant impact on the predicted binding affinities.</p>","PeriodicalId":99,"journal":{"name":"Physical Chemistry Chemical Physics","volume":null,"pages":null},"PeriodicalIF":2.9000,"publicationDate":"2024-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.rsc.org/en/content/articlepdf/2024/cp/d4cp01804d?page=search","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Physical Chemistry Chemical Physics","FirstCategoryId":"92","ListUrlMain":"https://pubs.rsc.org/en/content/articlelanding/2024/cp/d4cp01804d","RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"CHEMISTRY, PHYSICAL","Score":null,"Total":0}
引用次数: 0
Abstract
As a contribution to the understanding and rationalization of methodological and modeling effects in recent host–guest SAMPL challenges, using an alchemical molecular dynamics technique we have examined the impact of force field parameterization and ionic strength in connection with guest charge neutralization on computed dissociation free energies in two typical SAMPL heavily charged macrocyclic hosts encapsulating small protonated amines with disparate binding affinities. We have shown that the methodological treatment for host neutralization, with explicit ions or with the background neutralizing plasma in the context of alchemical calculations under periodic boundary conditions, has a moderate effect on the calculated affinities. On the other hand, we have shown that seemingly small differences in the force field parameterization in highly symmetric hosts can produce systematic effects on the structural features that can have a significant impact on the predicted binding affinities.
期刊介绍:
Physical Chemistry Chemical Physics (PCCP) is an international journal co-owned by 19 physical chemistry and physics societies from around the world. This journal publishes original, cutting-edge research in physical chemistry, chemical physics and biophysical chemistry. To be suitable for publication in PCCP, articles must include significant innovation and/or insight into physical chemistry; this is the most important criterion that reviewers and Editors will judge against when evaluating submissions.
The journal has a broad scope and welcomes contributions spanning experiment, theory, computation and data science. Topical coverage includes spectroscopy, dynamics, kinetics, statistical mechanics, thermodynamics, electrochemistry, catalysis, surface science, quantum mechanics, quantum computing and machine learning. Interdisciplinary research areas such as polymers and soft matter, materials, nanoscience, energy, surfaces/interfaces, and biophysical chemistry are welcomed if they demonstrate significant innovation and/or insight into physical chemistry. Joined experimental/theoretical studies are particularly appreciated when complementary and based on up-to-date approaches.