Friday, December 19, 2025 12/19/2025

Next generation implicit solvation for atomistic modeling

Award Number: R01GM144596
ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 01/01/2022
PERIOD OF PERFORMANCE END DATE: 03/31/2026

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Next generation implicit solvation for atomistic modeling - Project Summary. This proposal responds to PAR-19-253 “Focused Technology Research and Development”. Our main goal is to develop a novel class of implicit solvation models, as accurate, and even more accurate, than standard explicit solvent models, but much faster. The high accuracy, fast implicit solvation models will be combined with several innovative strategies to deliver new computational protocols to improve accuracy and speed of binding free energies prediction, directly relevant to drug design. We will develop a computational tool for fast screening of existing and potential multiple simultaneous mutations in the SARS-CoV-2 coronavirus genome for high affinity to human cells, which translates into high infectivity. Progress in modern bio-molecular sciences, from structural biology to structure-based drug design, is greatly accelerated by atomic-level modeling and simulations that bridge the gap between theory and experiment. The so-called implicit solvation models can provide critical advantages in speed and versatility through representing the effects of solvent – often the most computationally expensive part of such simulations – in a particularly efficient manner. The resulting speed-up of modeling efforts is critical in many areas such as protein folding or protein-ligand docking; however, the accuracy of the current fast models does not reach the standard of the more traditional, but computationally very demanding explicit solvent approach. As a result, prediction reliability of the practical, fast implicit solvation models remains low. In general, high accuracy is a prerequisite for quantitative in-silico drug design. Here, the accuracy limitation of the current implicit solvation framework will be addressed in a novel, systematic way; advantages of the new implicit solvation models will be demonstrated in the context of improving the accuracy of protein-ligand binding free energy calculations. We will use a novel approach to systematically add most of the missing explicit solvation effects to the very basic, but computationally efficient implicit solvation framework of the Poisson and generalized Born (GB) models, with little computational overhead. The GB model is particularly well suited for molecular dynamics simulations. We have set high accuracy standards for the new theory: one kT (thermal noise) deviation from experiment for small molecules hydration, which is better than what most widely used explicit water models, such as TIP3P, can currently deliver. Based on preliminary results, this goal is within reach. The high accuracy combined with the expected computational efficiency will usher in the next generation of implicit solvation models that can make a profound difference in bio-medically relevant atomistic calculations. Example of an immediate impact: Close to, or better than, “industry standard” accuracy in protein- ligand binding calculations, but at a significantly reduced computational expense. Example of a long term impact: Fast, versatile computational tools to analyze binding of viruses to host cells will increase our preparedness for future pandemics.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = $0 )
2026	2025	VIRGINIA POLYTECHNIC INSTITUTE & STATE UNIVERSITY	300 TURNER ST NW	BLACKSBURG	VA	24060	MONTGOMERY	USA	Biomedical Research and Research Training	000	4	11/5/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2025 ( Subtotal = $302,817 )
2025	2025	VIRGINIA POLYTECHNIC INSTITUTE & STATE UNIVERSITY	300 TURNER ST NW	BLACKSBURG	VA	24060	MONTGOMERY	USA	Biomedical Research and Research Training	001	4	8/5/2025	NON-COMPETING CONTINUATION	$30,281
2025	2025	VIRGINIA POLYTECHNIC INSTITUTE & STATE UNIVERSITY	300 TURNER ST NW	BLACKSBURG	VA	24060	MONTGOMERY	USA	Biomedical Research and Research Training	000	4	12/19/2024	NON-COMPETING CONTINUATION	$272,536
														Subtotal = $302,817

Issue Date FY: 2024 ( Subtotal = $342,634 )
2024	2024	VIRGINIA POLYTECHNIC INSTITUTE & STATE UNIVERSITY	300 TURNER ST NW	BLACKSBURG	VA	24060	MONTGOMERY	USA	Biomedical Research and Research Training	002	3	8/21/2024	SUPPLEMENT FOR EXPANSION	$44,647
2024	2024	VIRGINIA POLYTECHNIC INSTITUTE & STATE UNIVERSITY	300 TURNER ST NW	BLACKSBURG	VA	24060	MONTGOMERY	USA	Biomedical Research and Research Training	001	3	6/18/2024	NON-COMPETING CONTINUATION	$29,799
2024	2024	VIRGINIA POLYTECHNIC INSTITUTE & STATE UNIVERSITY	300 TURNER ST NW	BLACKSBURG	VA	24060	MONTGOMERY	USA	Biomedical Research and Research Training	000	3	12/20/2023	NON-COMPETING CONTINUATION	$268,188
														Subtotal = $342,634

Issue Date FY: 2023 ( Subtotal = $303,804 )
2023	2023	VIRGINIA POLYTECHNIC INSTITUTE & STATE UNIVERSITY	300 TURNER ST NW	BLACKSBURG	VA	24060	MONTGOMERY	USA	Biomedical Research and Research Training	001	2	2/21/2023	NON-COMPETING CONTINUATION	$30,381
2023	2023	VIRGINIA POLYTECHNIC INSTITUTE & STATE UNIVERSITY	300 TURNER ST NW	BLACKSBURG	VA	24060	MONTGOMERY	USA	Biomedical Research and Research Training	000	2	12/15/2022	NON-COMPETING CONTINUATION	$273,423
														Subtotal = $303,804

Issue Date FY: 2022 ( Subtotal = $294,013 )
2022	2022	VIRGINIA POLYTECHNIC INSTITUTE AND STATE UNIVERSITY	300 TURNER ST NW STE 4200	BLACKSBURG	VA	24061	MONTGOMERY	USA	Biomedical Research and Research Training	000	1	12/27/2021	NEW	$294,013
														Subtotal = $294,013

Grand Total All Awards = $1,243,268

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Next generation implicit solvation for atomistic modeling

Award Number: R01GM144596

ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 01/01/2022

PERIOD OF PERFORMANCE END DATE: 03/31/2026

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