Carbohydrates are the most abundant biopolymers on earth. Their biological functions include fuels, energy storage, metabolic intermediates, structural roles and, importantly, molecular recognition. Accordingly, detailed knowledge of carbohydrate structure-function relationships will allow for better understanding of a variety of biological phenomena as well as facilitate the development of therapeutic agents and energy technologies. To explore such structure-function relationships theoretical approaches offer great potential. The proposed study will expand and improve theoretical methods for the study of carbohydrates, including those involved in molecular recognition, and improve our understanding of the structural and dynamical properties of these important molecules, including the role of solvation on those properties. These goals will be achieved by extending the additive empirical force field developed in our laboratory during the initial funding period to furanose containing disaccharides, glycoproteins and glycolipids, and carbohydrates that include non-hydroxyl functional groups. Force fields developments efforts will also initiate the optimization of a polarizable force field based on the classical Drude oscillator and include development of a 5-point polarizable water model. The proposed force fields will then be validated on a series of di-, tri and polysaccharides, glycoproteins and glycolipids. A variety of experimental data is available for the targeted molecules and the proposed calculations will also yield insights into the properties of these biologically important systems. Upon completion of the proposed study validated additive and polarizable force fields for carbohydrates will be available to the scientific community that are compatible with available force fields for proteins, lipids and nucleic acids. The availability of these tools will greatly enhance the applicability of computational approaches to these biologically essential molecules, facilitating the development of novel therapeutic agents, vaccines, approaches to clean energy and counterterrorism agents.
Carbohydrate's biological functions include fuels, energy storage, metabolic intermediates, structural roles and molecular recognition. The proposed study will develop new computational models for carbohydrates that will allow for studies on the structural and dynamical properties at a molecular level of detail. These tools will facilitate the development of novel therapeutic agents, vaccines, approaches to clean energy and counterterrorism agents.
|Baliban, Scott M; Yang, Mingjun; Ramachandran, Girish et al. (2017) Development of a glycoconjugate vaccine to prevent invasive Salmonella Typhimurium infections in sub-Saharan Africa. PLoS Negl Trop Dis 11:e0005493|
|Lemkul, Justin A; MacKerell Jr, Alexander D (2017) Polarizable Force Field for DNA Based on the Classical Drude Oscillator: I. Refinement Using Quantum Mechanical Base Stacking and Conformational Energetics. J Chem Theory Comput 13:2053-2071|
|Small, Meagan C; Aytenfisu, Asaminew H; Lin, Fang-Yu et al. (2017) Drude polarizable force field for aliphatic ketones and aldehydes, and their associated acyclic carbohydrates. J Comput Aided Mol Des 31:349-363|
|Yang, Mingjun; Huang, Jing; Simon, Raphael et al. (2017) Conformational Heterogeneity of the HIV Envelope Glycan Shield. Sci Rep 7:4435|
|Yang, Mingjun; Simon, Raphael; MacKerell Jr, Alexander D (2017) Conformational Preference of Serogroup B Salmonella O Polysaccharide in Presence and Absence of the Monoclonal Antibody Se155-4. J Phys Chem B 121:3412-3423|
|Lemkul, Justin A; MacKerell Jr, Alexander D (2017) Polarizable Force Field for DNA Based on the Classical Drude Oscillator: II. Microsecond Molecular Dynamics Simulations of Duplex DNA. J Chem Theory Comput 13:2072-2085|
|Jo, Sunhwan; Cheng, Xi; Lee, Jumin et al. (2017) CHARMM-GUI 10 years for biomolecular modeling and simulation. J Comput Chem 38:1114-1124|
|Khan, Hanif M; Grauffel, Cédric; Broer, Ria et al. (2016) Improving the Force Field Description of Tyrosine-Choline Cation-? Interactions: QM Investigation of Phenol-N(Me)4+ Interactions. J Chem Theory Comput 12:5585-5595|
|Chauhan, Jamal; Cardinale, Steven; Fang, Lei et al. (2016) Towards Development of Small Molecule Lipid II Inhibitors as Novel Antibiotics. PLoS One 11:e0164515|
|Lakkaraju, Sirish Kaushik; Lemkul, Justin A; Huang, Jing et al. (2016) DIRECT-ID: An automated method to identify and quantify conformational variations--application to ?2 -adrenergic GPCR. J Comput Chem 37:416-25|
Showing the most recent 10 out of 81 publications