Chitra Narayanan - Academia.edu (original) (raw)

Papers by Chitra Narayanan

PURPOSE. Many forms of congenital hereditary cataract are associated with mutations in the crysta... more PURPOSE. Many forms of congenital hereditary cataract are associated with mutations in the crystallin genes. The authors focus attention on congenital lamellar cataract, which is associated with the R168W mutation in ␥C-crystallin, and congenital zonular pulverulent cataract, which is associated with a 5-bp insertion in the ␥C-crystallin gene.

Protein Science, 2007

The homochirality, or isotacticity, of the natural amino acids facilitates the formation of regul... more The homochirality, or isotacticity, of the natural amino acids facilitates the formation of regular secondary structures such as α-helices and β-sheets. However, many examples exist in nature where novel polypeptide topologies use both l- and d-amino acids. In this study, we explore how stereochemistry of the polypeptide backbone influences basic properties such as compactness and the size of fold space by simulating both lattice and all-atom polypeptide chains. We formulate a rectangular lattice chain model in both two and three dimensions, where monomers are chiral, having the effect of restricting local conformation. Syndiotactic chains with alternating chirality of adjacent monomers have a very large ensemble of accessible conformations characterized predominantly by extended structures. Isotactic chains on the other hand, have far fewer possible conformations and a significant fraction of these are compact. Syndiotactic chains are often unable to access maximally compact states available to their isotactic counterparts of the same length. Similar features are observed in all-atom models of isotactic versus syndiotactic polyalanine. Our results suggest that protein isotacticity has evolved to increase the enthalpy of chain collapse by facilitating compact helical states and to reduce the entropic cost of folding by restricting the size of the unfolded ensemble of competing states.

Protein Science, 2008

Replica exchange molecular dynamics simulations are used to generate three ensembles of an S-pept... more Replica exchange molecular dynamics simulations are used to generate three ensembles of an S-peptide analog (AETAAAKFLREHMDS). Percent helicity of the peptide ensembles calculated using STRIDE is compared to percent helicity calculated from 13Cα chemical shift deviations (CSD) from random coil in order to test the assumption that CSD can be correlated to percent helicity. The two estimates of helicity, one based on structure and the other on CSD, are in close to quantitative agreement, except at the edges of helical stretches where disagreements of as much as 50% can be found. These disagreements can occur by CSDs both as an under- and an overestimate of peptide helicity. We show that underestimation arises due to ensemble averaging of positive CSDs from conformers with torsion angles in the helical region of Ramachandran space with negative CSDs corresponding to conformers of the peptide in the extended region. In contrast, overestimation comes about due to the fact that a large number of conformations with torsion angles in the helical region are not counted as helical by STRIDE due to a lack of correlated helical torsion angles in neighboring residues.

Journal of The American Chemical Society, 2007

Replica exchange molecular dynamics simulations are used to generate a set of 20 structural ensem... more Replica exchange molecular dynamics simulations are used to generate a set of 20 structural ensembles between 270 and 690 K for the G peptide corresponding to residues 41−56 of the B1 domain of protein G. Each of the structural ensembles is then compared with ...

Journal of Molecular Biology, 2009

PURPOSE. Many forms of congenital hereditary cataract are associated with mutations in the crysta... more PURPOSE. Many forms of congenital hereditary cataract are associated with mutations in the crystallin genes. The authors focus attention on congenital lamellar cataract, which is associated with the R168W mutation in ␥C-crystallin, and congenital zonular pulverulent cataract, which is associated with a 5-bp insertion in the ␥C-crystallin gene.

Protein Science, 2007

The homochirality, or isotacticity, of the natural amino acids facilitates the formation of regul... more The homochirality, or isotacticity, of the natural amino acids facilitates the formation of regular secondary structures such as α-helices and β-sheets. However, many examples exist in nature where novel polypeptide topologies use both l- and d-amino acids. In this study, we explore how stereochemistry of the polypeptide backbone influences basic properties such as compactness and the size of fold space by simulating both lattice and all-atom polypeptide chains. We formulate a rectangular lattice chain model in both two and three dimensions, where monomers are chiral, having the effect of restricting local conformation. Syndiotactic chains with alternating chirality of adjacent monomers have a very large ensemble of accessible conformations characterized predominantly by extended structures. Isotactic chains on the other hand, have far fewer possible conformations and a significant fraction of these are compact. Syndiotactic chains are often unable to access maximally compact states available to their isotactic counterparts of the same length. Similar features are observed in all-atom models of isotactic versus syndiotactic polyalanine. Our results suggest that protein isotacticity has evolved to increase the enthalpy of chain collapse by facilitating compact helical states and to reduce the entropic cost of folding by restricting the size of the unfolded ensemble of competing states.

Protein Science, 2008

Replica exchange molecular dynamics simulations are used to generate three ensembles of an S-pept... more Replica exchange molecular dynamics simulations are used to generate three ensembles of an S-peptide analog (AETAAAKFLREHMDS). Percent helicity of the peptide ensembles calculated using STRIDE is compared to percent helicity calculated from 13Cα chemical shift deviations (CSD) from random coil in order to test the assumption that CSD can be correlated to percent helicity. The two estimates of helicity, one based on structure and the other on CSD, are in close to quantitative agreement, except at the edges of helical stretches where disagreements of as much as 50% can be found. These disagreements can occur by CSDs both as an under- and an overestimate of peptide helicity. We show that underestimation arises due to ensemble averaging of positive CSDs from conformers with torsion angles in the helical region of Ramachandran space with negative CSDs corresponding to conformers of the peptide in the extended region. In contrast, overestimation comes about due to the fact that a large number of conformations with torsion angles in the helical region are not counted as helical by STRIDE due to a lack of correlated helical torsion angles in neighboring residues.

Journal of The American Chemical Society, 2007

Replica exchange molecular dynamics simulations are used to generate a set of 20 structural ensem... more Replica exchange molecular dynamics simulations are used to generate a set of 20 structural ensembles between 270 and 690 K for the G peptide corresponding to residues 41−56 of the B1 domain of protein G. Each of the structural ensembles is then compared with ...

Journal of Molecular Biology, 2009