00693nas a2200133 4500008004100000022001400041245018100055210006900236260008000305300000900385490000800394100002500402856013200427 2013 eng d a0006-349500aCompetition between adsorption and intrinsic collapse of full-length a beta 1-42 on the surface of a single-walled carbon nanotube: insights from molecular dynamics simulations0 aCompetition between adsorption and intrinsic collapse of fulllen a600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USAbBiophys SoccJAN a508A0 v1041 aSengupta, Neelanjana uhttps://library.ncl.res.in/content/competition-between-adsorption-and-intrinsic-collapse-full-length-beta-1-42-surface-single-002204nas a2200169 4500008004100000022001400041245015900055210006900214260011000283300001200393490000700405520142700412100001901839700001901858700002501877856013201902 2013 eng d a1463-907600aCritical roles of key domains in complete adsorption of a beta peptide on single-walled carbon nanotubes: insights with point mutations and MD simulations0 aCritical roles of key domains in complete adsorption of a beta p aTHOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLANDbROYAL SOC CHEMISTRYcNOV a837-8440 v153 a

Owing to the influence of nanomaterials on biomacromolecular behavior, their potential applications are rapidly gaining attention. Based on atomistic molecular dynamics simulation studies we have recently reported that the full-length A beta peptide, whose self-assembly is associated with Alzheimer's disease, adsorbs rapidly on single-walled carbon nanotubes, thereby losing its natural propensity to collapse. Here, we investigate the mechanistic overlap between the peptide's compactification and its adsorption, while decoupling the roles of hydrophobicity and aromaticity via point mutations. The collapse mechanism is correlated with interactions between the central hydrophobic core (HP1) and the peptide's C-terminal domain, which are almost exactly compensated by interactions arising from the nanotube after complete adsorption. Adsorption is initiated by HP1 and consolidated by strong interactions arising from the N-terminal domain. Altering the hydrophobicity, but not the aromatic character, of the central residue in HP1 decreases the collapse probability. On the other hand, the adsorption propensity is dramatically reduced when either the hydrophobicity or the aromatic character in HP1 is compromised. The hydrophobicity of HP1 is responsible for dewetting transitions that facilitate its initial interactions with the nanotube, which then lead to very favorable interactions with the nanotube.

1 aJana, Asis, K.1 aJose, Jaya, C.1 aSengupta, Neelanjana uhttps://library.ncl.res.in/content/critical-roles-key-domains-complete-adsorption-beta-peptide-single-walled-carbon-nanotubes-002706nas a2200169 4500008004100000022001400041245013100055210006900186260009100255300002600346490000600372520195800378100001902336700002402355700002502379856013202404 2014 eng d a1932-620300aCross dimerization of amyloid-beta and alpha synuclein proteins in aqueous environment: a molecular dynamics simulations study0 aCross dimerization of amyloidbeta and alpha synuclein proteins i a1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USAbPUBLIC LIBRARY SCIENCEcSEP aArticle No. : e1068830 v93 a

Self-assembly of the intrinsically unstructured proteins, amyloid beta (A beta) and alpha synclein (alpha Syn), are associated with Alzheimer's Disease, and Parkinson's and Lewy Body Diseases, respectively. Importantly, pathological overlaps between these neurodegenerative diseases, and the possibilities of interactions between A beta and alpha Syn in biological milieu emerge from several recent clinical reports and in vitro studies. Nevertheless, there are very few molecular level studies that have probed the nature of spontaneous interactions between these two sequentially dissimilar proteins and key characteristics of the resulting cross complexes. In this study, we have used atomistic molecular dynamics simulations to probe the possibility of cross dimerization between alpha Syn(1-95) and A beta(1-42), and thereby gain insights into their plausible early assembly pathways in aqueous environment. Our analyses indicate a strong probability of association between the two sequences, with inter-protein attractive electrostatic interactions playing dominant roles. Principal component analysis revealed significant heterogeneity in the strength and nature of the associations in the key interaction modes. In most, the interactions of repeating Lys residues, mainly in the imperfect repeats `KTKEGV' present in alpha Syn(1-95) were found to be essential for cross interactions and formation of inter-protein salt bridges. Additionally, a hydrophobicity driven interaction mode devoid of salt bridges, where the non-amyloid component (NAC) region of alpha Syn(1-95) came in contact with the hydrophobic core of A beta(1-42) was observed. The existence of such hetero complexes, and therefore hetero assembly pathways may lead to polymorphic aggregates with variations in pathological attributes. Our results provide a perspective on development of therapeutic strategies for preventing pathogenic interactions between these proteins.

1 aJose, Jaya, C.1 aChatterjee, Prathit1 aSengupta, Neelanjana uhttps://library.ncl.res.in/content/cross-dimerization-amyloid-beta-and-alpha-synuclein-proteins-aqueous-environment-molecular-001984nas a2200169 4500008004100000022001400041245006200055210006200117260007100179300001400250490000800264520138100272100002501653700002501678700002101703856009001724 2016 eng d a1520-610600aConformational energy landscape of the ritonavir molecule0 aConformational energy landscape of the ritonavir molecule a1155 16TH ST, NW, WASHINGTON, DC 20036 USAbAMER CHEMICAL SOCcMAY a4331-43400 v1203 a

Conformational polymorphism of ritonavir, a well-known pharmaceutical drug, is intricately linked to its efficacy in the treatment of acquired immunodeficiency syndrome (AIDS). Polymorphic transition from the crystalline form I to form II leads to the loss of bioactivity. The constituent ritonavir molecules adopt a trans configuration about the carbamate torsion angle in the form I crystal, and a cis configuration in the form II crystal. Investigating the energetics and mechanistic features of conformational transitions at the single molecule level is a key step toward decoding the complex features of the solid state polymorphism. In this work, we employ the energy landscape framework to investigate the conformational transitions of an isolated ritonavir molecule. The landscape is explored using discrete path sampling (DPS) and visualized in terms of disconnectivity graphs. We identify two distinct funnels corresponding to the two molecular forms that are identified by crystallography. The two regions can be reliably distinguished using the carbamate torsion angle, and the corresponding interconversion rates are predicted to follow Arrhenius behavior. The results provide mechanistic insight into pathways for cis <-> trans interconversion at the molecular level and may also help in elucidating the polymorphic transitions in the crystal state.

1 aChakraborty, Debayan1 aSengupta, Neelanjana1 aWales, David, J. uhttps://library.ncl.res.in/content/conformational-energy-landscape-ritonavir-molecule00624nas a2200157 4500008004100000245010600041210007000147260000800217300001600225490000700241100001900248700001900267700002500286700002600311856012900337 2016 eng d00aConformational features of the Aβ42 peptide monomer and its interaction with the surrounding solvent0 aConformational features of the Aβ42 peptide monomer and its inte cOCT a30144-301590 v181 aKhatua, Prabir1 aJose, Jaya, C.1 aSengupta, Neelanjana1 aBandyopadhyay, Sanjoy uhttps://library.ncl.res.in/content/conformational-features-a%CE%B242-peptide-monomer-and-its-interaction-surrounding-solvent01730nas a2200157 4500008004100000022001400041245010500055210006900160260000900229300001400238490000700252520114200259100001701401700002501418856012901443 2019 eng d a1948-718500aCold thermal response of an amyloid oligomer differs from typical globular protein cold denaturation0 aCold thermal response of an amyloid oligomer differs from typica cMAY  a2453-24570 v103 a

In contrast with the general behavior of folded proteins, the cold thermal response of amyloid assemblies is difficult to elicit with simple models. We exploit exhaustive simulations to evaluate the thermal response of a barrel-shaped model amyloid oligomer, with a distinct hydrophobic core akin to that of folded proteins. Cumulative thermal data over the range of 210-483 K indicate a sharp inflection and rise in structural stability as the temperature is decreased below the melting temperature of the water model. This is not commensurate with the equilibrium free energy profile obtained with core packing as the order parameter. However, energetic analyses and the size of their fluctuations indicate the crucial role of hydration in mediating structural transitions, beyond the expected temperature-dependent hydrophobic effect. Structural ordering of the hydration layer over bulk water is maximized at the transition and vanishes at high temperatures. This is a first direct demonstration of the microscopic influence of hydration water on the low-temperature response of an amyloid assembly close to the cryo-regime.

1 aMenon, Sneha1 aSengupta, Neelanjana uhttps://library.ncl.res.in/content/cold-thermal-response-amyloid-oligomer-differs-typical-globular-protein-cold-denaturation