D. Shukla

Mechanistic Basis for Enhanced Strigolactone Sensitivity in KAI2 Triple Mutant

The paper uses molecular dynamics simulations to show how specific mutations in KAI2 enhance strigolactone sensitivity by stabilizing binding and increasing pocket volume.

Binding Position Dependent Modulation of Smoothened Activity by Cyclopamine

This study uses simulations to show cyclopamine acts as an agonist when bound to the CRD of Smoothened and as an antagonist when bound to the TMD, with mixed effects when bound to both sites.

Characterization of binding kinetics and intracellular signaling of new psychoactive substances targeting cannabinoid receptor using transition-based reweighting method

This study uses simulation and machine learning to analyze how new psychoactive substances interact with cannabinoid receptors, revealing structural differences that lead to stronger beta-arrestin signaling and adverse effects.

Functional Regulation of Aquaporin Dynamics by Lipid Bilayer Composition

This study shows how lipid bilayer composition affects the dynamics and function of the plant aquaporin SoPIP2;1 using molecular dynamics simulations.

An inimitable proprotein convertase subtilisin kexin-9 (PCSK9) cleavage site VFAQ on Spike protein along with furin cleavage site makes SARS-CoV-2 unique

The paper identifies a novel PCSK9 cleavage site in SARS-CoV-2 Spike protein and suggests its combination with the furin site contributes to the virus's uniqueness in pathogenicity and drug development.

The Sequence Basis for Selectivity of Ephrin-B2 Ligand for Eph Receptors and Pathogenic Henipavirus G Glycoproteins

This paper identifies sequence changes in Ephrin-B2 that enhance its binding to henipavirus glycoproteins over Eph receptors, enabling the design of neutralizing decoy receptors.

Active Learning of the Conformational Ensemble of Proteins using Maximum Entropy VAMPNets

This paper introduces MaxEnt VAMPNet, an active learning method that accelerates conformational landscape exploration in biomolecules by maximizing entropy in VAMPNet-trained microstates.

Sequence Controlled Secondary Structure Determines Site-selectivity of Lanthipeptides

This study shows that the secondary structure of lanthipeptide substrates determines site-selectivity and ring formation order, independent of the dehydration step.

Atomistic Insights Into The Mechanism of Dual Affinity Switching In Plant Nitrate Transporter NRT1.1

The paper uses simulations to explain how phosphorylation regulates dual-affinity switching in the plant nitrate transporter NRT1.1 by stabilizing transport states and decoupling dimer dynamics.

AtSWEET13 transporter discriminates sugars by selective facial and positional substrate recognition

This study identifies how AtSWEET13 discriminates between glucose and sucrose through facial and positional substrate recognition during transport.

Distinct Activation Mechanisms Regulate Subtype Selectivity of Cannabinoid Receptors

This study identifies conformational differences between CB1 and CB2 receptors that explain the subtype selectivity of CB2 selective agonists.

Contribution of Signaling Partner Association to Strigolactone Receptor Selectivity

This study uses molecular dynamics to show that ShHTL7 has enhanced MAX2 binding due to its T2-T3 helix structure, contributing to its higher signaling activity compared to other strigolactone receptors.

Effect of Histidine Covalent Modification on Strigolactone Receptor Activation and Selectivity

This study shows that covalent butenolide modification of histidine enhances strigolactone receptor activation, with greater effect in the parasitic ShHTL7 receptor.

The Effects of N-linked Glycosylation on SLC6 Transporters

This study uses molecular dynamics simulations to investigate how N-linked glycosylation affects the dynamics of four human SLC6 transporters, finding no consistent structural impact but altered extracellular loop dynamics.

Understanding Supramolecular Assembly of Supercharged Proteins

This study investigates the supramolecular assembly of oppositely supercharged proteins using experiments and modeling, showing that surface charge distribution and net charge determine assembly behavior and stability.

Elevator-type Mechanism of the Cyanobacterial Bicarbonate Transporter

This study uses molecular dynamics simulations to elucidate the conformational dynamics of the cyanobacterial bicarbonate transporter BicA and identify mutations that lower the free energy barrier for transport.

Activation Mechanism of the Human Smoothened Receptor

This study reveals the activation mechanism of the human Smoothened receptor using molecular dynamics simulations, showing a stage-wise movement of transmembrane helices and a hydrophobic tunnel for cholesterol transport.

Multi-Agent Reinforcement Learning-based Adaptive Sampling for Conformational Sampling of Proteins

This paper introduces two multi-agent reinforcement learning algorithms to improve conformational sampling in protein simulations by coordinating agents to share information and prioritize relevant collective variables.

Mapping Strigolactone Hydrolysis in DWARF14 via QM/MM String Method

This study uses QM/MM simulations to investigate the mechanism of strigolactone hydrolysis by DWARF14, finding the acyl substitution pathway is favored and covalent modifications are dynamic.

Activation Mechanism of Strigolactone Receptors And Its Impact On Ligand Selectivity Between Host And Parasitic Plants

This study uses molecular dynamics simulations to show that ShHTL7 and AtD14 adopt active conformations without ligand, but ShHTL7 has a higher population in the inactive state due to sequence differences affecting binding pocket closure.

Machine learning guided design of high affinity ACE2 decoys for SARS-CoV-2 neutralization

The paper uses machine learning to design high-affinity ACE2 decoys for SARS-CoV-2 neutralization, identifying double mutants with binding affinity comparable to a previously known triple mutant.

Engineered High-Affinity ACE2 Peptide Mitigates ARDS and Death Induced by Multiple SARS-CoV-2 Variants

This study shows an engineered ACE2 peptide effectively mitigates ARDS and death in mice infected with multiple SARS-CoV-2 variants.

Dual role of strigolactone receptor signaling partner in inhibiting substrate hydrolysis

This study uses molecular dynamics simulations to show that the CTH of D3 stabilizes inactive conformations of D14 and blocks SL binding, inhibiting strigolactone signaling.

OPTN limits herpes stromal keratitis severity and demyelination through negative regulation of IL-17 and hyperinflammatory T-cell response

The paper investigates how OPTN reduces HSV-1-induced HSK severity and demyelination by suppressing IL-17 and hyperinflammatory T-cell responses in a mouse model.

Structural rearrangement of the intracellular gate of the serotonin transporter induced by Thr276 phosphorylation

This study uses molecular dynamics simulations to show that Thr276 phosphorylation reduces free energy barriers for SERT to transition to the inward-facing state, enhancing serotonin transport.

Predicting the Activities of Drug Excipients on Biological Targets using One-Shot Learning

This study uses one-shot learning to predict interactions between drug excipients and biological targets, finding many excipients can interact with targets and affect their function.

Intriguing Role of Water in Plant Hormone Perception

This study uses molecular dynamics simulations to show that water displacement at plant hormone receptor binding sites affects binding free energy and provides insights for agrochemical design.

Investigation of gating in outer membrane porins provides new perspectives on antibiotic resistance mechanisms

This study uses molecular dynamics simulations and experiments to show that dynamic gating of E. coli outer membrane porin OmpF, mediated by conserved acidic residues, regulates antibiotic permeability and contributes to antibiotic resistance.

Why does Δ9-Tetrahydrocannabinol act as a partial agonist of cannabinoid receptors?

This study investigates the molecular mechanism of partial agonism in cannabinoid receptors, finding that THC stabilizes both agonist and antagonist-like poses through its alkyl side chain, leading to partial receptor activation.

Deep Mutagenesis of a Transporter for Uptake of a Non-Native Substrate Identifies Conformationally Dynamic Regions

This study uses deep mutagenesis to identify mutations enhancing APP+ import by SERT, revealing conformational dynamics and mutationally tolerant regions along the permeation pathway.