Areas of Expertise (7)
Simulations of Biological Systems
Hydration Phenomena at Interfaces and Nanosystems
Dr. Shekhar Garde is the Dean of Engineering and the Elaine and Jack Parker Chaired Professor at Rensselaer Polytechnic Institute.
Garde received his B. Chem. Eng. (University of Bombay, 1992) and Ph.D. (U. Delaware, 1997) in Chemical Engineering. He was a Director’s post-doctoral fellow at Los Alamos National Laboratory from 1997 to 1999. He joined Rensselaer in 1999 as an Assistant Professor, and was promoted to Associate in 2004, and to Full Professor in 2006. He was appointed the Parker Chaired Professor in 2006, and as the Head of Chemical and Biological Engineering Department in 2007 and served in that role for seven years before becoming the Dean of Engineering.
Dr. Garde’s research employs statistical mechanical theory and molecular modeling and simulation tools to understand the role of water in biological interactions. He has published ~100 peer-reviewed papers in leading scientific journals, which have been cited over 8300 times (H=46, per Google Scholar). He has given over 140 invited talks at leading universities, industries, and international conferences, including many keynote lectures. He has received several awards including the CAREER Award by the US National Science Foundation (2001), School of Engineering Research Award (2003), Rensselaer Early Career Award (2004), and the 2011 Robert W. Vaughan Lecturer-ship at California Institute of Technology. He was elected a Fellow of the American Institute of Medical and Biological Engineers (2014) and of American Association for Advancement of Science (2015).
Dr. Garde co-leads the Molecularium Project, which aims to excite children about the world of atoms and molecules. He has pioneered integration of data from large-scale molecular dynamics simulations into Disney-Pixar style animations. He is a co-executive producer of the Molecularium movie – Molecules to the MAX – 2D and 3D IMAX as well as DVD versions of which are currently being distributed nationwide. In 2011 Garde was honored with the Explore~Imagine~Discover Award by the Children’s Museum of Science and Technology, in the Capital District, NY. The Nanospace portal of the Molecularium project received ‘Best of the Web’ award in Education by Center for Digital Education in 2013.
University of Delaware: Ph.D., Chemical Engineering 1997
University of Bombay: B.Chem.Eng., Chemical Engineering 1992
Media Appearances (3)
Rensselaer engineering dean talks focusing on diversity in STEM fields
Albany Business Review online
Shekhar Garde is the dean of the nationally ranked School of Engineering at Rensselaer Polytechnic Institute in Troy, New York.
The New York Times Opinion online
Shekhar Garde is an Indian-born chemical engineer at Rensselaer Polytechnic Institute. He studies the role of water in the creation of life and is a pioneer in animating molecular dynamics, producing a 3-D Imax film called “Molecules to the Max.”
Shekhar Garde Named Dean of Engineering at Rensselaer Polytechnic Institute
Rensselaer Polytechnic Institute today named Shekhar Garde as dean of the School of Engineering. The appointment is effective July 1. Garde, the Elaine S. and Jack S. Parker Chaired Professor in Engineering at Rensselaer, has served since 2007 as head of the university’s Howard. P. Isermann Department of Chemical and Biological Engineering (CBE).
The Effects of Ligand Structure on Protein-Multimodal Ligand InteractionsBiophysical Journal
Camille Bilodeau, Edmond Y Lau, Steve Cramer, Shekhar Garde
2019 Many important biophysical phenomena are driven by the structuring of water around solutes. Solutes perturb the structure ( i.e., the packing and orientational organization) of water molecules in the vicinity - the extent of the perturbation depending on the nature of solute and strength of solute-water interactions - resulting in solute-solute interactions that are strongly mediated by water. Although the role of water in mediating solute-solute interactions has been well characterized for simple systems, such as small ions or simple hydrophobic solutes, most biological systems are larger and more complex molecules that contain regions of mixed charge, hydrophobicity, hydrogen bonding, and other modes of interaction. Here, we focus on the role of water in governing the behavior of small, flexible molecules containing multiple modes of interaction (e.g., charge, hydrophobicity, and hydrogen bonding interactions) and how this behavior impacts their interactions with proteins. In particular, we study a set of multimodal chromatographic ligands which are commonly used for protein separation applications. We characterize the conformational and hydration preferences of each ligand in water including water density fluctuations in the solvation shell. By decomposing ligand contributions intramolecular versus water-mediated parts, we quantify the role of water in ligand conformational equilibria. We also perform molecular simulations of multimodal ligands in aqueous solutions with different proteins. We find that regardless of which region of the protein surface the ligand binds to, its conformational preferences in free solution are maintained upon binding. Finally, we identify ligand design characteristics that lead to differences in the overall strength of protein-ligand interactions. This work provides a basis for characterizing the role that water plays in governing protein-ligand interactions as well as serves to guide the design of new multimodal ligands for protein separations.
Hydrophobicity of proteins and nanostructured solutes is governed by topographical and chemical contextProceedings of the National Academy of Sciences
Erte Xi, Vasudevan Venkateshwaran, Lijuan Li, Nicholas Rego, Amish J. Patel, and Shekhar Garde
2017 Numerous biological self-assembly processes, from protein folding to molecular recognition, are driven by hydrophobic interactions, yet characterizing hydrophobicity at the nanoscale has remained a major challenge, because it requires understanding of the strength of protein–water interactions and the ease with which they can be disrupted. Water near a protein responds to its chemistry and topography in a manner that is collective and complex and cannot be captured by commonly used surface area models or hydropathy scales. We demonstrate that water density fluctuations near proteins can characterize protein hydrophobicity and reveal its dependence on curvature and chemical patterns at the nanoscale. Our approach opens new avenues for understanding and efficient characterization of biomolecular interactions.
Arginine mutations in antibody complementarity-determining regions display context-dependent affinity/specificity trade-offsJournal of Biological Chemistry
Kathryn E Tiller, Lijuan Li, Sandeep Kumar, Mark C Julian, Shekhar Garde, Peter M Tessier
2017 Antibodies commonly accumulate charged mutations in their complementarity-determining regions (CDRs) during affinity maturation to enhance electrostatic interactions. However, charged mutations can mediate non-specific interactions, and it is unclear to what extent CDRs can accumulate charged residues to increase antibody affinity without compromising specificity. This is especially concerning for positively charged CDR mutations that are linked to antibody polyspecificity. To better understand antibody affinity/specificity trade-offs, we have selected single-chain antibody fragments specific for the negatively charged and hydrophobic Alzheimer's amyloid β peptide using weak and stringent selections for antibody specificity. Antibody variants isolated using weak selections for specificity were enriched in arginine CDR mutations and displayed low specificity. Alanine-scanning mutagenesis revealed that the affinities of these antibodies were strongly dependent on their arginine mutations. Antibody variants isolated using stringent selections for specificity were also enriched in arginine CDR mutations, but these antibodies possessed significant improvements in specificity. Importantly, the affinities of the most specific antibodies were much less dependent on their arginine mutations, suggesting that over-reliance on arginine for affinity leads to reduced specificity. Structural modeling and molecular simulations reveal unique hydrophobic environments near the arginine CDR mutations. The more specific antibodies contained arginine mutations in the most hydrophobic portions of the CDRs, whereas the less specific antibodies contained arginine mutations in more hydrophilic regions. These findings demonstrate that arginine mutations in antibody CDRs display context-dependent impacts on specificity and that affinity/specificity trade-offs are governed by the relative contribution of arginine CDR residues to the overall antibody affinity.