The computational chemistry and protein modeling team in the Advanced Biomedical Computational Science (ABCS) group provides novel solutions in structural modeling and computational chemistry. Computational scientists in the group collaborate with NCI researchers by using and developing quantum chemistry, molecular mechanics/molecular dynamics (MM/MD), and DNA/protein structure prediction methods for various modeling research areas, including but not limited to protein and nucleotide properties, drug interactions and drug design.
Expertise includes:
- Protein and nucleic acids modeling
- Protein dynamics.
- Characterization of RNA dynamics (conformational stability or multiple functional states).
- Protein structure determination.
- Variant effects on structure/modeling the impact of protein mutations.
- RNA modeling (from sequence to 3D structure).
- Modeling protein-protein, protein-nucleic acids, and protein-ligand interactions.
- Drug target binding.
- RNA targeting with small molecules.
- Biologics design.
- Machine learning- and rational-based biomolecular design.
- Molecular dynamics simulations.
- Alanine scan mutagenesis.
- Post translational modifications.
- Evolutionary relationships.
- Computational chemistry
- Computation of biomolecular reaction mechanisms, pathways and energetics.
- Prediction of fluorescence and bioluminescence spectra and other spectroscopic properties.
- Accurate partial atomic charges.
- Effects of varying substituents upon chemistry (transition states, activities).
- Covalent binding affinities of inhibitors.
- Drug structures and isomeric energies including interconversion barriers.
- Predictions of product distributions.
- Determining modes of activity.
- Kinetic properties, acidity, and reactivities.
- Wave function analysis.
- Molecular electrostatic potential maps and other molecular properties.
- Structural modeling tools
- Protein structure prediction: AlphaFold2/3, ESMFold, Colabfold
- Protein force fields: AMBER, CHARMM
- Nucleic Acids force fields: AMBER
- Molecular dynamics (MD) programs: AMBER, NAMD
- Molecular visualization: PyMol, VMD, Chimera
- Protein, DNA, and RNA/ligand binding: AutoDock/Vina, VM2
- Protein sequence, structure, and function design: RFDiffusion, ProteinMPNN
- Quantum chemical calculations: GAMESS
Recent Publications:
- Designing fluorophores and bioluminescent agents for biomedical imaging (Caldwell, … Ivanic, Love, Malvar, Mills, Prescher, and Schnermann 2024, J Org Chem., PMID 38096133; Love, … Ivanic, Schnermann, Prescher, 2023, JACS, PMID 36745536; Daly, … Ivanic, and Schnermann, 2022, Photochemistry and Photobiology, PMID 34676539; Bandi, … Ivanic, Bruns, and Schnermann, 2022, Nat Methods, PMID 35228725; Usama, … Ivanic, and Schnermann, Biosens Bioelectron, 2022, PMID 36137483).
- Development of massively parallel computational chemistry methods (Zahariev, … Ivanic, et al., 2023, J Chem Theory Comput., PMID 37793073).
- Performing molecular dynamics simulations to quantify effects of genetic variants on WDR44 structure and dynamics (Accogli, Shakya, Yang, Insinna, Kim, Bell, et al., 2024, Nat Communications, PMID 38191484).
- Performing free energy perturbation calculations and in silico mutagenesis approaches to design enhanced-reactive pHLA-TCR antigens for Type 1 diabetes antigen immunotherapy applications (Song, Bell, et al., 2023, Proc Natl Acad Sci U S A, PMID 37040399).
- Modeling the energetics of covalent drug/warhead binding to cysteine residues (Byun, … Ivanic, … Yoo, 2023, JACS, PMID 37183434).
- Modeling the impact of glycosylation on self-assembly of peptide hydrogels (Lopez-Silva, …Bell, Suarez Alvarez, Kasprzak, Shi, Schneider, 2024, Mater., DOI: 10.1021/acs.chemmater.4c00291).
- Combining NMR, Molecular Dynamics, and in vitro binding assays to identify a site in pre-genomic RNA crucial to the hepatitis B virus (HBV) replication and a drug from the FDA-approved compound library as a selective ligand targeting it. (Olenginski, Kasprzak, et al., 2023, Molecules, PMID 36838792; LeBlanc, Kasprzak, … Ivanic, Schneekloth Jr., Shapiro, Dayie, and Le Grice, 2022, J Biomol Struct Dyn., PMID 34155954).
- Development of a protocol to overcome limitations of ligand docking prediction programs with additional Molecular Dynamics (MD) simulations to explore multiple conformations of the targeted RNAs prior to docking and evaluate stability of the predicted docking poses. (Kasprzak, Shapiro, 2023, Methods Mol Biol., PMID: 36227563).
- Determining binding affinities of gliadin epitopes to human leukocyte antigens (HLAs) to confirm the association of HLA-DQ2.5 to an increased risk of celiac disease (Song, Lee, Bell, Goudey, and Zhou, 2022, J Phys Chem B., PMID 35796490)
- Reviewing experimental findings and molecular dynamics calculations to understand the interaction of graphene nanosheets and its interaction with proteins, lipid membranes, and DNA (Chen, Bell, and Luan, 2022, Adv Drug Deliv Rev., 2022, PMID 35597306)
To learn more about the available support and/or to request a project consultation, please reach out to Dr. Brian Luke (brian.luke@nih.gov) or submit a request online (https://abcs-amp.nih.gov/project/request/ABCS/). Please note that you must be logged in to the NIH network to access and submit the online project request link.