Chemistry, Physical and Theoretical Chemistry, Spectroscopy, Biophysics
34
Scopus Publications
Scopus Publications
Redox-Dependent Vibrational Energy Flow in Amicyanin Revealed by Molecular Dynamics Simulations Serlin Nirmala Grazy Chinnappan, Ramachandran Gnanasekaran Journal of Physical Chemistry B, 2026 Understanding how redox events influence intraprotein energy flow is essential for elucidating the dynamical basis of biological electron transfer. Here, we investigate redox-dependent vibrational energy redistribution in the type I copper protein amicyanin using atomistic molecular dynamics simulations combined with time-correlation and cross-correlation analyses of residue-resolved energy fluctuations. Energy-difference time series constructed for the Cu + and Cu 2+ states were used to characterize vibrational spectra, dynamical couplings, and ensemble-based energy-transfer pathways originating from the metal coordination sphere. Our analysis reveals that vibrational energy injected at the copper center propagates through a small subset of highly probable residue pathways that form a distributed communication network rather than a single dominant channel. Top-ranked pathways exhibit nearly identical efficiencies in the reduced and oxidized states, with representative pathway scores of ∼2.6 × 10 –2 for both Cu + and Cu 2+ . Across the ensemble of major pathways, efficiency ratios lie in the narrow range 0.95–1.02, indicating that changes in copper oxidation state modulate the amplitude of energetic fluctuations while preserving the underlying routes of energy propagation. Extension of this analysis to the amicyanin–cytochrome c 551 i interface reveals coherent interprotein coupling mediated by both residue–residue interactions and dynamically structured interfacial water. Hydrogen-bond lifetime analysis demonstrates that interfacial water exhibits confined, heterogeneous dynamics characteristic of protein–protein interfaces, providing a dynamical bottleneck that supports energy redistribution across the complex. Together, these results demonstrate that amicyanin employs a robust, preorganized vibrational communication network conserved under redox cycling, offering a mechanistic framework for reliable long-range dynamical coupling between local redox chemistry and global protein response.
Exploring the influence of water molecules on modulating the functional dynamics of amicyanin: a computational investigation Archan Ravi Sankar, Ramachandran Gnanasekaran Molecular Simulation, 2026 We investigated the dynamics of water molecules located in both the interior and hydration-shell regions of the amicyanin protein using molecular dynamics simulations. Our analysis indicates that water molecules interacting with residues along the proposed electron transport pathways contribute to pathway-specific hydration environments that modulate local solvent exposure and hydrogen-bond dynamics, thereby influencing the dynamical landscape surrounding the charge transfer route. Pathway-specific hydration was found to modulate hydrogen-bond stability, solvent exposure, and dynamical persistence, indicating that water contributes to heterogeneous relaxation behaviour across the protein. Overall, our results suggest that hydration water plays an active and spatially selective role in shaping the charge transport pathway from the copper center of amicyanin toward the iron center of cytochrome, highlighting the importance of solvent–protein coupling in biological electron transfer.
Atomic Ordered Functionalization by Covalent and Noncovalent Interactions for Glycine Detection in Armchair Graphene Nanoribbons─A Theoretical Approach Manasa Bhat, Kaustab Ghosh, Ramachandran Gnanasekaran ACS Omega, 2025 High Resolution Image Download MS PowerPoint Slide This study investigates the covalent and noncovalent functionalization (CF and NCF) of glycine (Gly) on armchair graphene nanoribbons (AGNR 42 and AGNR 54 ) at different sites (bulk, single edge, and double edge) using density functional theory (DFT) at the B3LYP/6-311++G(d,p) level. For covalent bonding, two different attachment modes of Gly ( O and N sites) were considered. Key sensing parameters such as adsorption energy ( E ad ), band gap ( E g ), density of states (DOS), charge transfer, electrical conductivity, molecular electrostatic potential (MEP), sensitivity, and recovery time were analyzed. The results show that covalent bonding enhances sensitivity due to strong chemical attachment, while noncovalent bonding enables quicker recovery due to weak physical interactions. Although AGNR 54 has a larger surface area, AGNR 42 demonstrates better sensitivity with CF. The configurations, such as NCF-Gly-SEAGNR 42, NCF-Gly-DEAGNR 42, NCF-Gly-SEAGNR 54, O -Gly-BFAGNR 54, and N -Gly-BFAGNR 54, exhibit fast recovery times of 1.599 × 10 –12 s, 6.15 × 10 –4 s, 76 s, 595 s, and 5.293 × 10 6 s, respectively. Among these, N -Gly-BFAGNR 54, NCF-Gly-SEAGNR 54, and O -Gly-BFAGNR 54 exhibit intermediate sensing responses (0.223, 0.026, and 0.019, respectively) and acceptable recovery time. These findings further emphasize the relationship between sensitivity and reusability, where enhancing one often affects the other. The overall sensing performance is governed not only by the bonding type but also by the surface area, position of sites, adsorption site, adsorption energy, and the orientation of the analyte. Thus, the significant variation in adsorption and electronic properties of AGNRs reveals that atomic-order functionalization enhances the detection of Gly and may be considered a promising biosensor for Gly removal. This study also provides new evidence and deeper insights that advance the current understanding of GNR-based biosensing systems.
Computational insights into novel inhibitors: virtual screening of small molecules against human carbonic anhydrase II Sermarajan Arunachalam, Balamurali M. M., Ramachandran Gnanasekaran Frontiers in Chemistry, 2025 Carbonic anhydrases, zinc-based metalloproteins, facilitate the reversible conversion of CO2 into carbonic acid when transported through blood vessels and subsequently regulate the physiological pH. In humans, this enzyme has been the therapeutic target for numerous diseases, as its abnormal regulation leads to a variety of disorders. The regulatory mechanism of this enzyme includes targeting catalytic Zn2+ ions as well as the residues that significantly regulate the protein’s structure and stability. With the available data on numerous sulfonamides, sulfamates, sulfamides, and non-sulfamide-derived inhibitors, in this study, a library of sulfonamide, extended aromatic sulfonamide, and non-sulfonamide derivatives was screened using a fragment-based drug discovery approach. Virtual screening was performed with molecular docking (DOCK 6 and Schrödinger GLIDE), rescored using MM-GBSA, and validated over 100-ns molecular dynamics simulations. Pharmacophore models were developed to identify key interaction features, while pharmacokinetic profiles were evaluated to assess their drug-likeness. Compounds S8 (sulfonamide) and S15–S16 (non-sulfonamides) emerged as promising inhibitors, showing strong Zn2+ coordination and stable binding to residues His93, Leu196, Thr197, and Thr198 that favor pharmacokinetic properties. The results provide atomistic insights into carbonic anhydrase II (CAII) inhibition and identify potential leads for further experimental validation.
Conformational Stability and Vibrational Relaxation as a Function of Halogen Substitution in Benzene sulfonamides: A Theoretical Study Ramachandran Gnanasekaran, Hari Datt Pandey Chemistryselect, 2024 Studying the vibrational energy flow within molecules can help us better understand their reactivity and facilitate the design of novel functional groups for potential drug candidates. This study examined the conformation of benzene sulfonamide in solvents and vacuum. Potential energy surfaces were computed for the two possible conformations, showing that the conformers’ stability varied with the medium. Additionally, the vibrational energy redistribution of halogen‐substituted benzene sulfonamide conformers was studied in solvents and vacuums. The lifetimes of the halogen stretching mode C−X (where X=F, Cl, or Br) in the substituted benzene sulfonamides were calculated and compared. The solvent and vacuum media lifetimes followed the order: C−Cl>C−Br>C−F. However, the degree of delocalization of vibrational energy was found to vary between them.
Utilizing Baylis–Hillman Adducts Followed by Michael Addition/Elimination Reaction for the Synthesis of Unusual Conformationally Stable Molecules Governed by Aromatic Interactions Vishal Prasad Sharma, Vipin Kumar, Priyanka Sonker, Priyanka Yadav, Rashmi Singh, Ramachandran Gnanasekaran, Ashish Kumar Tewari European Journal of Organic Chemistry, 2023 The compounds under investigation sought a new approach to synthesis via the Baylis‐Hillman (B−H) and Michael addition reactions. The product formation‘s legitimacy was tested using a repeat reaction with many different nucleophiles. The additional stability of the product via aromatic π⋅⋅⋅π and C−H⋅⋅⋅π interactions may result in unexpected product formation in diverse reactions undertaken utilizing different starting materials. This study suggests that weak interaction not only provides selectivity during reactions but also modifies the result.
The first HyDRA challenge for computational vibrational spectroscopy Taija L. Fischer, Margarethe Bödecker, Sophie M. Schweer, Jennifer Dupont, Valéria Lepère, Anne Zehnacker-Rentien, Martin A. Suhm, Benjamin Schröder, Tobias Henkes, Diego M. Andrada, Roman M. Balabin, Haobam Kisan Singh, Himangshu Pratim Bhattacharyya, Manabendra Sarma, Silvan Käser, Kai Töpfer, Luis I. Vazquez-Salazar, Eric D. Boittier, Markus Meuwly, Giacomo Mandelli, Cecilia Lanzi, Riccardo Conte, Michele Ceotto, Fabian Dietrich, Vicente Cisternas, Ramachandran Gnanasekaran, Michael Hippler, Mahmoud Jarraya, Majdi Hochlaf, Narasimhan Viswanathan, Thomas Nevolianis, Gabriel Rath, Wassja A. Kopp, Kai Leonhard, Ricardo A. Mata Physical Chemistry Chemical Physics, 2023
Using rattling ions to probe sub-ps water network dynamics Diedrich A. Schmidt, Ozgur Birer, Stefan Funkner, Benjamin P. Born, Ramachandran Gnanasekaran, Gerhard W. Schwaab, David M. Leitner, Martina Havenith Irmmw Thz 2010 35th International Conference on Infrared Millimeter and Terahertz Waves Conference Guide, 2010
