Development and benchmarking of Open Force Field v1.0.0, the Parsley small molecule force field

Yudong Qiu, Daniel Smith, Simon Boothroyd, Hyesu Jang, Jeffrey Wagner, Caitlin C Bannan, Trevor Gokey, Victoria T Lim, Chaya Stern, Andrea Rizzi, Xavier Lucas, Bryon Tjanaka, Michael R Shirts, Michael Gilson, John D. Chodera, Christopher I Bayly, David Mobley, Lee-Ping Wang
Preprint ahead of publication: [chemRxiv] [force fields] [Open Force Field Initiative]

We present a new, modern small molecule force field for molecular design from the Open Force Field Initiative, a large industry-academic collaboration that focuses on open science, open data, and modern open source infrastructure.

Assessing the accuracy of octanol-water partition coefficient predictions in the SAMPL6 Part II log P Challenge

Mehtap Işık, Teresa Danielle Bergazin, Thomas Fox,  Andrea Rizzi, John D. Chodera, and David L. Mobley.
Journal of Computer Aided Molecular Design, 34:335, 2020. [DOI] [PDF] [bioRxiv] [GitHub]

We report the performance assessment of the 91 methods that were submitted to the SAMPL6 blind challenge for predicting octanol-water partition coefficient (logP) measurements. The average RMSE of the most accurate five MM-based, QM-based, empirical, and mixed approach methods based on RMSE were 0.92±0.13, 0.48±0.06, 0.47±0.05, and 0.50±0.06, respectively.

The SAMPL6 SAMPLing challenge: Assessing the reliability and efficiency of binding free energy calculations

Andrea Rizzi, Travis Jensen, David R. Slochower, Matteo Aldeghi, Vytautas Gapsys, Dimitris Ntekoumes, Stefano Bosisio, Michail Papadourakis, Niel M. Henriksen, Bert L. de Groot, Zoe Cournia, Alex Dickson, Julien Michel, Michael K. Gilson, Michael R. Shirts, David L. Mobley, and John D. Chodera
Journal of Computer Aided Molecular Design 34:601, 2020. [DOI] [PDF] [bioRxiv] [GitHub]

To assess the relative efficiencies of alchemical binding free energy calculations, the SAMPL6 SAMPLing challenge asked participants to submit predictions as a function of computer effort for the same force field and charge model. Surprisingly, we found that most molecular simulation codes cannot agree on the binding free energy was, even for the same force field.

Small-molecule targeting of MUSASHI RNA-binding activity in acute myeloid leukemia

Gerard Minuesa, Steven K Albanese, Arthur Chow, Alexandra Schurer, Sun-Mi Park, Christina Z. Rotsides, James Taggart, Andrea Rizzi, Levi N. Naden, Timothy Chou, Saroj Gourkanti, Daniel Cappel, Maria C Passarelli, Lauren Fairchild, Carolina Adura, Fraser J Glickman, Jessica Schulman, Christopher Famulare, Minal Patel, Joseph K Eibl, Gregory M Ross, Derek S Tan, Christina S Leslie, Thijs Beuming, Yehuda Goldgur, John D Chodera, Michael G Kharas
Nature Communications 10:2691, 2019. [DOI] [bioRxiv] [GitHub] [MSKCC blog post]

We use absolute alchemical free energy calculations to identify the likely interaction site for a small hydrophobic ligand that shows activity against MUSASHI in AML.

Overview of the SAMPL6 host-guest binding affinity prediction challenge

Andrea Rizzi, Steven Murkli, John N. McNeill, Wei Yao, Matthew Sullivan, Michael K. Gilson, Michael W. Chiu, Lyle Isaacs, Bruce C. Gibb, David L. Mobley*, John D. Chodera*
* denotes co-corresponding authors
Journal of Computer-Aided Molecular Design special issue on SAMPL6, 32:937, 2018. [DOI] [bioRxiv] [GitHub]

We present an overview of the host-guest systems and participant performance for the SAMPL6 host-guest blind affinity prediction challenges, assessing how well various physical modeling approaches were able to predict ligand binding affinities for simple ligand recognition problems where receptor sampling and protonation state effects are eliminated due to the simplicity of supramolecular hosts. We find that progress is now stagnated likely due to force field limitations.