OPLS3e: Extending Force Field Coverage for Drug-Like Small Molecules

Katarina Roos; Chuanjie Wu; Wolfgang Damm; Mark Reboul; James Stevenson; Chao Lü; Markus K. Dahlgren; Sayan Mondal; Wei Chen; Lingle Wang; Robert Abel; Richard A. Friesner; Edward Harder

doi:10.1021/acs.jctc.8b01026

Abstract

Building upon the OPLS3 force field we report on an enhanced model, OPLS3e, that further extends its coverage of medicinally relevant chemical space by addressing limitations in chemotype transferability. OPLS3e accomplishes this by incorporating new parameter types that recognize moieties with greater chemical specificity and integrating an on-the-fly parametrization approach to the assignment of partial charges. As a consequence, OPLS3e leads to greater accuracy against performance benchmarks that assess small molecule conformational propensities, solvation, and protein-ligand binding.

Keywords

Force field (fiction)Computer scienceField (mathematics)DrugNanotechnologyData scienceMaterials scienceMedicinePharmacologyArtificial intelligenceMathematics

Affiliated Institutions

Related Publications

OPLS4: Improving Force Field Accuracy on Challenging Regimes of Chemical Space

Edward Harder , Chao Lü , Chuanjie Wu +10 more

We report on the development and validation of the OPLS4 force field. OPLS4 builds upon our previous work with OPLS3e to improve model accuracy on challenging regimes of drug-li...

2021 Journal of Chemical Theory and Comput... 1577 citations

CHARMM fluctuating charge force field for proteins: II Protein/solvent properties from molecular dynamics simulations using a nonadditive electrostatic model

Sandeep Patel , Alexander D. MacKerell , Charles L. Brooks

Abstract A fluctuating charge (FQ) force field is applied to molecular dynamics simulations for six small proteins in explicit polarizable solvent represented by the TIP4P‐FQ po...

2004 Journal of Computational Chemistry 448 citations

Optimized Molecular Dynamics Force Fields Applied to the Helix−Coil Transition of Polypeptides

Robert B. Best , Gerhard Hummer

Obtaining the correct balance of secondary structure propensities is a central priority in protein force-field development. Given that current force fields differ significantly ...

2009 The Journal of Physical Chemistry B 879 citations

Determination of Electrostatic Parameters for a Polarizable Force Field Based on the Classical Drude Oscillator

Victor M. Anisimov , Guillaume Lamoureux , Igor Vorobyov +3 more

A procedure to determine the electrostatic parameters has been developed for a polarizable empirical force field based on the classical Drude oscillator model. Atomic charges an...

2004 Journal of Chemical Theory and Comput... 311 citations

Integrated Modeling Program, Applied Chemical Theory (IMPACT)

Jay L. Banks , Hege S. Beard , Yixiang Cao +15 more

Abstract We provide an overview of the IMPACT molecular mechanics program with an emphasis on recent developments and a description of its current functionality. With respect to...

2005 Journal of Computational Chemistry 1445 citations

Publication Info

Year: 2019
Type: article
Volume: 15
Issue: 3
Pages: 1863-1874
Citations: 1176
Access: Closed

External Links

View on DOI.org

Social Impact

Altmetric

OPLS3e: Extending Force Field Coverage for Drug-Like Small Molecules

PlumX Metrics

Social media, news, blog, policy document mentions

Citation Metrics

1176

OpenAlex

Cite This

APA Style

                            
                                
                                    Katarina Roos, 
                                
                                    Chuanjie Wu, 
                                
                                    Wolfgang Damm
                                
                                et al.
                            
                            (2019). 
                            OPLS3e: Extending Force Field Coverage for Drug-Like Small Molecules. 
                            Journal of Chemical Theory and Computation
                            , 15
                            (3)
                            , 1863-1874.
                            https://doi.org/10.1021/acs.jctc.8b01026
                        

Identifiers

DOI: 10.1021/acs.jctc.8b01026