Postdoctoral position: Biopolymer force fields

The Open Force Field Consortium is seeking a postdoctoral fellow to work on the development of biopolymer (protein and potentially nucleic acid) force fields and supporting infrastructure for biopolymer parameterization and benchmarking.

POSITION DESCRIPTION

The Open Force Field Initiative is a network of academic and industry researchers working together to advance science and infrastructure required for building the next generation of small molecule and biomolecular force fields, and to improve predictive power of computational drug discovery techniques. The overarching aim is to develop automated and systematic data-driven techniques to parameterize and assess these new generations of more accurate force fields. We started with development of small molecule force fields and underlying open source infrastructure, resulting in a release of three optimized versions of Open Force Fields (codename Parsley). Each new release demonstrated improvements in accuracy and the performance of the latest release (OpenFF-1.2.0) is comparable to the commonly used public and commercial force fields, according to the used benchmarking data. Our preliminary internal benchmarks and a recent study suggest that using OpenFF-1.0.0 to model ligands in protein-ligand binding affinity calculations already displays significant progress toward reaching ~1 kcal/mol accuracy in ΔG for fixed-charge force fields. To further improve accuracy and to enable flexible support for covalent inhibitors and post-translational modifications, we now aim to co-optimize small molecule and protein parameters to produce a fully self-consistent force field. Both funding and key infrastructure components are in place to enable this effort, though it’s important to note that this position is pending final funding approval (expected in Oct/Nov 2020).

The main responsibilities associated with this position include:

• Prototyping an automated procedure for consistent small molecule and protein/biopolymer force field parameterization;
• Running complete co-optimization of all force field parameters to produce a fully consistent small molecule and protein force field (based on AMBER ff14SB);
• Developing extensive benchmarking protocols of protein force fields against experimental data (in collaboration with biopolymer force field communities, and the OpenFF Initiative and Consortium Advisory Boards)
• Selecting and wrangling appropriate QM and experimental datasets for training and benchmarking;
• Building necessary infrastructure in collaboration with our software scientists;
• Interaction and coordination with other team members and external stakeholders (pharma partners, other biopolymer force field communities, and similar).

Many aspects of this position can be tailored to accommodate the candidate’s expertise and ambitions for their further career development. Some of the additional opportunities include close collaboration with the Folding@Home team, as a power user of their infrastructure and/or as a contributor to infrastructure development. The candidate is expected to attend all relevant team meetings and the annual Open Force Field Consortium workshops. Attending any other events relevant to their work, such as conferences, workshops and other training programs, is highly encouraged. This position would be funded by The Open Force Field Consortium.

Desired qualifications:

• Experience with force field parameterization and benchmarking practices, preferably biopolymer force fields;
• Comfortable with the Python programming language;
• Exposure to modern open source software development practices (GitHub, unit tests, continuous integration);
• Good multidisciplinary teamwork and communication skills.

Bonus qualifications (nice to have, but not required):

• Experience with force field parameter fitting for small organic molecules;
• Experience with cheminformatics or computer-aided drug discovery;
• Knowledge of physical organic chemistry;
• Experience with high-performance computing clusters and/or cloud computing;
• Experience with the open-source GPU-accelerated molecular simulation Python library OpenMM;
• Experience with databases and distributed computing.

ABOUT US

As mentioned above, the Open Force Field Initiative is a wider network of academic and industry researchers bound by the mutual aim of making force fields better and building open source infrastructure. The core team consists of PhD students, postdocs and software scientists led by 4 academic PIs: John Chodera, Mike Gilson, David Mobley, and Michael Shirts. The postdocs and PhD students do research and exploratory/prototyping work around data selection and tool building requirements in collaboration with a team of software scientists who are focused on infrastructure development, support and maintenance. More about our current achievements and future plans can be found in the Open Force Field Initiative Executive Summary.

The Open Force Field Initiative is built around open source, open data, and open science principles. We aim to publish frequently and openly and a sample of existing publications can be found here. All of our software is released under permissive licenses and we try to share all data produced in our efforts. We also release frequent scientific updates on our website and on GitHub, and we have annual meetings with our pharma partners to give updates on our progress. In addition to this and other events, the OpenFF Initiative provides access to a large network of young and established scientists in computational chemistry from academia and industry, offering access to both academic and industry career paths. Supporting all team members in achieving their career goals is taken seriously by all OpenFF PIs.

LOCATION

The OpenFF Initiative offers a certain amount of location flexibility and the Open Force Field postdocs can be hosted at any of the participating investigator sites, but in this case, the preference would be given to the Chodera/Gilson/Mobley labs:

• John D. Chodera (MSKCC, New York City, NY)
• Michael K. Gilson (UCSD, La Jolla, CA)
• David L. Mobley (UCI, Irvine, CA)
• Michael R. Shirts (University of Colorado, Boulder, CO)

Due to the relocation and traveling complications arising from the COVID-19 outbreak, the OpenFF Initiative would consider remote work options for suitable candidates at their desired location.

APPOINTMENT DURATION

The initial appointment will be for one year, with the potential for extension to multiple years to focus on other aspects of force field science and engineering. This position is funded by the Open Force Field Consortium and it is pending final approval of funding in October or November 2020. The preferred starting date would be in early 2021.