Saturday, August 30, 2025 8/30/2025

Multiscale Modeling of Enzymatic Reactions and Bioimaging Probes

Award Number: R35GM153297
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: 06/01/2024
PERIOD OF PERFORMANCE END DATE: 05/31/2029

Group Awards By:

View Award Description

Multiscale Modeling of Enzymatic Reactions and Bioimaging Probes - Multiscale Modeling of Enzymatic Reactions and Bioimaging Probes Abstract This project addresses a critical technology/software gap — the accessibility of ab initio quantum mechan- ical molecular mechanical (QM/MM) multiscale modeling tools in the enzymology and bioimaging ﬁelds — by developing machine-learning-based and physics-based electronic structure and molecular simulation methods. In our R01 funding period, we made several methodological advances, especially (a) the ﬁrst !-learning poten- tial for simulating the enzyme reaction free energy (as demonstrated with the modeling of chorismate mutase catalysis), (b) an advance to the multiple time-step free energy simulation methodology, and (c) an analysis tool for interpreting/predicting the substitution effect on chromophore emission wavelength based on chromophore- substituent orbital interactions. Building on these method developments, we will further develop robust active-learning protocols for training !-learning potentials for ground and excited electronic states for systems in the macromolecular or solvent en- vironments. These !-learning potentials, when validated against advanced physics-based models, will enable routine (a) enzyme reaction simulations and (b) optoacoustic and other bioimaging probe modeling in our lab and the larger community. CRISPR-Cas proteins will be used as our primary test enzyme systems. We will employ the !-learning potentials in molecular dynamics simulations and seek an atomistic understanding of (a) the effect of SpyCas9 conformational changes on HNH- and RuvC-domain catalyzed DNA cleavage activity, and (b) the mechanism of AsCas12a and FnCas12a RuvC-domain catalyzed non-target strand DNA cleavage. For bioimaging probes, we will seek general guiding principles for designing optoacoustic imaging probes. It will be achieved by performing ab initio-QM/MM-quality multiscale modeling to explore the impact of struc- tural modiﬁcations (especially the attachment of halogen atoms and ﬂexible alkane chains) on the molecular absorbance and nonradiative decay rate, both key factors in the optoacoustic signal generation.


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: 2025 ( Subtotal = $352,487 )
2025	2025	UNIVERSITY OF OKLAHOMA	660 PARRINGTON OVAL RM 301	NORMAN	OK	73019	CLEVELAND	USA	Biomedical Research and Research Training	001	2	7/21/2025	NON-COMPETING CONTINUATION	$352,487
2025	2024	UNIVERSITY OF OKLAHOMA	660 PARRINGTON OVAL RM 301	NORMAN	OK	73019	CLEVELAND	USA	Biomedical Research and Research Training	000	1	11/7/2024	NEW	$0
														Subtotal = $352,487

Issue Date FY: 2024 ( Subtotal = $394,119 )
2024	2024	UNIVERSITY OF OKLAHOMA	660 PARRINGTON OVAL RM 301	NORMAN	OK	73019	CLEVELAND	USA	Biomedical Research and Research Training	000	1	5/17/2024	NEW	$394,119
														Subtotal = $394,119

Grand Total All Awards = $746,606

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Multiscale Modeling of Enzymatic Reactions and Bioimaging Probes

Award Number: R35GM153297

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: 06/01/2024

PERIOD OF PERFORMANCE END DATE: 05/31/2029

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer