# Collaborative Research: On calculating polar solvation and binding energies for non-rigid proteins in the Poisson-Boltzmann theory: modeling, analysis and application

> **NSF 01002526DB NSF RESEARCH & RELATED ACTIVIT** · Clemson University (SC) · $174,976

## Abstract

Electrostatic free energy (EFE) calculations are indispensable for the quantitative analysis of biological processes, as they characterize the polar interactions between charged biomolecules such as proteins, DNA and RNA, and their surrounding ionic solvent environments.  As one of the most widely used implicit solvent models, the Poisson-Boltzmann (PB) model computes EFE as the difference between PB energies of biomolecules in two reference states, typically vacuum and solvent. The success of classical PB theory relies on two restrictive assumptions: (i) biomolecules remain rigid and do not change shape when moving between states, and (ii) identical computational procedures are used for both states.  However, under physiological conditions, proteins are inherently flexible and undergo conformational changes during solvation and binding. This project aims to overcome the rigidity limitation by introducing a generalized PB theory that accommodates non-rigid biomolecular structures. This enables PB models to handle shape changes in key biological processes such as solvation and binding. The proposed algorithms will be implemented in DelPhi, an open-source PB package, and they will be applied to other popular PB solvers in the form of post-processing patches.  The new computational tools will be distributed free of charge to academic users, making them accessible to the broader biological research community. In addition, this project will provide interdisciplinary research and t

## Key facts

- **NSF award ID:** 2512105
- **Awardee organization:** Clemson University (SC)
- **SAM.gov UEI:** H2BMNX7DSKU8
- **PI:** Emil Alexov
- **Primary program:** 01002526DB NSF RESEARCH & RELATED ACTIVIT
- **All programs:** Biotechnology, EXP PROG TO STIM COMP RES, COMPUTATIONAL SCIENCE & ENGING
- **Estimated total:** $174,976
- **Funds obligated:** $174,976
- **Transaction type:** Standard Grant
- **Period:** 09/01/2025 → 08/31/2028

## Primary source

NSF Award Search: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2512105

## Citation

> US National Science Foundation, Award 2512105, Collaborative Research: On calculating polar solvation and binding energies for non-rigid proteins in the Poisson-Boltzmann theory: modeling, analysis and application. Retrieved via AI Analytics 2026-06-08 from https://api.ai-analytics.org/grant/nsf/2512105. Licensed CC0.

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