Dozens of researchers of the Open Force Field Initiative gathered for a group photo in San DiegoThe Open Force Field Initiative researchers gathered for their Consortium Workshop held in La Jolla, CA in January 2019. Photo courtesy the Open Force Field Initiative.

 

Published: June 30, 2020 By

There are four primary aims established in the grant proposal:
 
  • Aim 1: Create a modern, open software infrastructure for automatically generating and validating force fields and utilizing them broadly in modeling packages.
  • Aim 2: Construct open datasets and databases for next-generation force field development.
  • Aim 3: Develop Bayesian inference techniques to address key questions in force field physical modeling and predict systematic error.
  • Aim 4: Integrate the results of Aims 1-3 to construct and validate open source, transferable, and self-consistent force fields for small molecule interactions with complex biomolecular systems.

The National Institute of General Medical Sciences awarded nearly $2.5 million in funding over four years to the Open Force Field Initiative, an open source, open science and open data project co-founded by Associate Professor Michael Shirts.

Shirts is the principal investigator on the Focused Technology Research & Development R01 proposal, which established multiple ambitious goals to help build the project’s utility, efficacy and reach in developing new computational models for molecules to push forward the study of biomolecular phenomena.

“If we build this infrastructure, it will make it much easier for other researchers—likely hundreds across the globe—to do accurate calculations for molecular design problems like developing new drugs or engineering polymeric materials for batteries and other energy applications,” Shirts said.

Michael Shirts

Associate Professor Michael Shirts

In recent years, researchers have improved software and methods for modeling biophysical problems, specifically for how effectively pharmaceuticals behave. However, improvements in the force fields that operate at the core of these simulations have been slow in coming.

“The initiative aims to help molecular simulations reach their full potential, overcome their inaccuracies and limitations in small molecule design, accelerate and automate progress in force field development, and create statistically guided processes to advance the field,” Shirts said.

“The big motivation is that the molecular models used for biophysics and drug design didn't seem to be getting much better, and a lot of graduate student hours were chewed up making them,” Shirts said. “A new approach was needed, so four other researchers and I decided to start the effort. The infrastructure that we will develop will save many, many hours for a lot of people and make the process of developing molecular models much more of an engineering process, rather than an art like it typically is now.”

Shirts and his fellow researchers are grateful for the funding and looking forward to expanding the project. “We can now expand the project into co-developing computational models for biological models in combination with prospective drug molecules,” Shirts said. “This allows us to ask some of the longer-term scientific questions about molecular models that industrial funding to The Open Force Field Initiative didn’t really allow.”

The Open Force Field Initiative is a partnership between researchers at CU Boulder, Memorial Sloan Kettering Cancer Center, University of California, Irvine, University of California, San Diego and University of California, Davis with additional collaborations with the MolSSI QCArchive and the AMBER community and a number of pharmaceutical companies.