Krishnakumar M. Ravikumar

Case Western Reserve University

Author Statistics

Papers

Citation

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i-10 index

Research Trends

Author Order

Document Type

Co-Authors

Sichun Yang

Case Western Reserve University

Wei Huang

Case Western Reserve University

D. L. Cox

University of California, Davis

Wonmuk Hwang

Texas A&M University

Amanda Parker

United States Government Accountability Office

Michael D. Toney

University of California, Davis

Alvin T. Yeh

Texas A&M University

Maria D. R. Peralta

University of California, Davis

Catherine Sierra

University of California, Davis

Herbert Levine

Northeastern University

Cooperative Institutions

University of California, Davis

Case Western Reserve University

Texas A&M University

Clark University

Stanford University

University School

University of Chicago

Center for Theoretical Biological Physics

University of Canterbury

Argonne National Laboratory

Author Statistics

Papers

Citation

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A computational study of the role of hydration in the assembly of collagen and other biofilaments

Alvin T. Yeh Krishnakumar M. Ravikumar

Hydration is known to be crucial in biomolecular interactions including ligand binding and self-assembly. In our earlier studies we have shown the key role of water in stabilizing the specific parts of the collagen triple helix depending on the imino acid content. We further showed that the primary hydration shell around collagen could act as a lubricating layer aiding in collagen assembly. But key details on the structure and dynamics of water near protein surfaces and its role in protein-protein interactions remain unclear. In the current study we have developed a novel method to analyze hydration maps around peptides at 1-A resolution around three self-assembling filament systems with known structures, that respectively have hydrated (collagen), dry non-polar and dry polar (amyloid) interfaces. Using computer simulations, we calculate local hydration maps and hydration forces. We find that the primary hydration shells are formed all over the surface, regardless of the types of the underlying amino acids. The weakly oscillating hydration force arises from coalescence and depletion of hydration shells as two filaments approach, whereas local water diffusion, orientation, or hydrogen bonding events have no direct effect. Hydration forces between hydrated, polar, and non-polar interfaces differ in the amplitude and phase of the oscillation relative to the equilibrium surface separation. Therefore, water-mediated interactions between these protein surfaces ranging in character from 'hydrophobic' to 'hydrophilic,' have a common molecular origin based on the robustly formed hydration shells, which is likely applicable to a broad range of biomolecular assemblies whose interfacial geometry is similar in length scale to those of the present study. In a related study through simulations we show that the rate of tissue optical clearing by chemical agents correlated with the preferential formation of hydrogen bond bridges between agent and collagen. Hydrogen bond bridge formation disrupts the collagen hydration layer and facilitates replacement by a chemical agent to destabilize the tertiary structure of collagens thereby reducing light scattering. This study suggests that the clearing abiility of an alcohol not only depends on its molecular size, but also on the position of hydroxyl groups on its backbone.

Coalescence (physics)

Solvation shell

Source

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Structure of Water Hydration Around Collagen

Krishnakumar M. Ravikumar Wonmuk Hwang

We investigate the hydration structure of collagen using molecular dynamics simulations. The water density maximum, and orientation near the surface of collagen and their specificity to the proximal collagen sequence are clearly visible in our analysis. These results provide insights into the effect of hydration in collagen self-assembly, and more generally, the anomalous behavior of water near protein surfaces.

Surface structure

Collagen fibril

10.1115/nemb2010-13108

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Role of Water in Mediating the Interaction Between Collagens

Biophysical Journal (2010)

Krishnakumar M. Ravikumar Wonmuk Hwang

Angstrom

Collagen helix

Crystal (programming language)

Sphere packing

Helix (gastropod)

10.1016/j.bpj.2009.12.336

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Theoretical modeling of multiprotein complexes by iSPOT: Integration of small-angle X-ray scattering, hydroxyl radical footprinting, and computational docking

Journal of Structural Biology (2016)

Wei Huang Krishnakumar M. Ravikumar Marc Parisien Sichun Yang

Small-angle X-ray scattering

Footprinting

Docking (animal)

Multiprotein complex

DNA footprinting

10.1016/j.jsb.2016.08.001

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Citations (32)

Molecular dynamics-based strength estimates of beta solenoid proteins

Soft Matter (2017)

Amanda Parker Krishnakumar M. Ravikumar D. L. Cox

The use of beta solenoid proteins as functionalizable, nanoscale, self-assembling molecular building blocks may have many applications, including templating the growth of wires or higher-dimensional structures. By understanding their mechanical strengths, we can efficiently design the proteins for specific functions. We present a study of the mechanical properties of seven beta solenoid proteins using GROMACS molecular dynamics software to produce force/torque-displacement data, implement umbrella sampling of bending/twisting trajectories, produce Potentials of Mean Force (PMFs), extract effective spring constants, and calculate rigidities for two bending and two twisting directions for each protein. We examine the differences between computing the strength values from force/torque-displacement data alone and PMF data, and show how higher precision estimates can be obtained from the former. In addition to the analysis of the methods, we report estimates for the bend/twist persistence lengths for each protein, which range from 0.5-3.4 μm. We note that beta solenoid proteins with internal disulfide bridges do not enjoy enhanced bending or twisting strength, and that the strongest correlate with bend/twist rigidity is the number of hydrogen bonds per turn. In addition, we compute estimates of the Young's modulus (Y) for each protein, which range from Y = 3.5 to 7.2 GPa.

Solenoid

Rigidity (electromagnetism)

Flexural rigidity

Force Field

Elasticity

BETA (programming language)

Persistence length

10.1039/c7sm01070b

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Citations (2)

Region‐specific role of water in collagen unwinding and assembly

Proteins Structure Function and Bioinformatics (2008)

Krishnakumar M. Ravikumar Wonmuk Hwang

Conformational stability of the collagen triple helix affects its turnover and determines tissue homeostasis. Although it is known that the presence of imino acids (prolines or hydroxyprolines) confer stability to the molecule, little is known regarding the stability of the imino-poor region lacking imino acids, which plays a key role in collagen cleavage. In particular, there have been continuing debates about the role of water in collagen stability. We addressed these issues using molecular dynamics simulations on 30-residue long collagen triple helices, including a structure that has a biologically relevant 9-residue imino-poor region from type III collagen (PDB ID: 1BKV). A torsional map approach was used to characterize the conformational motion of the molecule that differ between imino-rich and imino-poor regions. At temperatures 300 K and above, unwinding initiates at a common cleavage site, the glycine-isoleucine bond in the imino-poor region. This provides a linkage between previous observations that unwinding of the imino-poor region is a requirement for collagenase cleavage, and that isolated collagen molecules are unstable at body temperature. We found that unwinding of the imino-poor region is controlled by dynamic water bridges between backbone atoms with average lifetimes on the order of a few picoseconds, as the degree of unwinding strongly correlated with the loss of water bridges, and unwinding could be either prevented or enhanced, respectively by enforcing or forbidding water bridge formation. While individual water bridges were short-lived in the imino-poor region, the hydration shell surrounding the entire molecule was stable even at 330 K. The diameter of the hydrated collagen including the first hydration shell was about 14 A, in good agreement with the experimentally measured inter-collagen distances. These results elucidate the general role of water in collagen turnover: water not only affects collagen cleavage by controlling its torsional motion, but it also forms a larger-scale lubrication layer mediating collagen self-assembly.

Imino acid

Collagen helix

Cleavage (geology)

10.1002/prot.22026

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Citations (59)

Coarse-Grained Simulations of Protein-Protein Association: An Energy Landscape Perspective

Biophysical Journal (2012)

Krishnakumar M. Ravikumar Wei Huang Sichun Yang

Energy landscape

Association (psychology)

Basis (linear algebra)

Metastability

Electrostatics

10.1016/j.bpj.2012.07.013

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Citations (53)

Fast-SAXS-Pro: A Unified Approach to Computing SAXS Profiles of DNA, RNA, Protein, and their Complexes

Biophysical Journal (2013)

Krishnakumar M. Ravikumar Wei Huang Sichun Yang

Small-angle X-ray scattering

Nucleic acid structure

10.1016/j.bpj.2012.11.1028

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Citations (16)

Fast-SAXS-pro: A unified approach to computing SAXS profiles of DNA, RNA, protein, and their complexes

The Journal of Chemical Physics (2013)

Krishnakumar M. Ravikumar Wei Huang Sichun Yang

A generalized method, termed Fast-SAXS-pro, for computing small angle x-ray scattering (SAXS) profiles of proteins, nucleic acids, and their complexes is presented. First, effective coarse-grained structure factors of DNA nucleotides are derived using a simplified two-particle-per-nucleotide representation. Second, SAXS data of a 18-bp double-stranded DNA are measured and used for the calibration of the scattering contribution from excess electron density in the DNA solvation layer. Additional test on a 25-bp DNA duplex validates this SAXS computational method and suggests that DNA has a different contribution from its hydration surface to the total scattering compared to RNA and protein. To account for such a difference, a sigmoidal function is implemented for the treatment of non-uniform electron density across the surface of a protein/nucleic-acid complex. This treatment allows differential scattering from the solvation layer surrounding protein/nucleic-acid complexes. Finally, the applications of this Fast-SAXS-pro method are demonstrated for protein/DNA and protein/RNA complexes.

Small-angle X-ray scattering

10.1063/1.4774148

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Citations (51)

Quantitative Mapping of Protein Structure by Hydroxyl Radical Footprinting-Mediated Structural Mass Spectrometry: A Protection Factor Analysis

Biophysical Journal (2015)

Wei Huang Krishnakumar M. Ravikumar Mark R. Chance Sichun Yang

Footprinting

DNA footprinting

Reactivity

10.1016/j.bpj.2014.11.013

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Citations (93)