R. E. Amaro

Breaking Down the Bottlebrush: Atomically-Detailed Structural Dynamics of Mucins

This study uses molecular dynamics simulations to explore the structural dynamics of mucins, revealing how O-glycosylation influences their bottlebrush-like conformation.

Allosteric modulation by the fatty acid site in the glycosylated SARS-CoV-2 spike

This paper uses D-NEMD simulations to study how the fatty acid site in the glycosylated SARS-CoV-2 spike modulates its structure and function, revealing allosteric networks and the role of glycans.

Simulation-Driven Design of Stabilized SARS-CoV-2 Spike S2 Immunogens

This study designs stabilized SARS-CoV-2 S2 immunogens using simulation-driven approaches, showing improved stability and immunogenicity.

Transmissible SARS-CoV-2 variants with resistance to clinical protease inhibitors

The paper identifies SARS-CoV-2 variants resistant to protease inhibitors nirmatrelvir and ensitrelvir, showing pre-existing resistance and potential for spread.

Glycoproteomic landscape and structural dynamics of TIM family immune checkpoints enabled by mucinase SmE

The paper uses a mucinase to analyze glycoproteomic features of TIM family proteins and shows how glycosylation affects their structure through molecular dynamics simulations.

Selectivity and ranking of tight-binding JAK-STAT inhibitors using Markovian milestoning with Voronoi tessellations

The paper ranks JAK2/STAT5 inhibitors based on kinetic properties using MMVT in SEEKR2 to explain their selectivity over JAK3.

Breathing and Tilting: Mesoscale simulations illuminate influenza glycoprotein vulnerabilities

This study uses mesoscale simulations to analyze the dynamics of influenza glycoproteins, revealing new antigenic states and a vulnerability site in neuraminidase.

Targeting N-Myc in Neuroblastoma with Selective Aurora Kinase A Degraders

This study develops a first-in-class Aurora-A/N-Myc degrader, HLB-0532259, which effectively reduces N-Myc levels and shows tumor reduction in neuroblastoma models.

Targeted protein S-nitrosylation of ACE2 as potential treatment to prevent spread of SARS-CoV-2 infection

This paper develops aminoadamantane nitrate compounds that inhibit SARS-CoV-2 infection by S-nitrosylating ACE2 and blocking viral entry, showing efficacy in vitro and in a Syrian hamster model.

Architecture and self-assembly of the jumbo bacteriophage nuclear shell

The paper identifies chimallin as the primary protein forming the bacteriophage nuclear shell and characterizes its self-assembly into closed compartments.

Elucidation of cryptic and allosteric pockets within the SARS-CoV-2 protease

The paper identifies cryptic and allosteric pockets in the SARS-CoV-2 main protease using enhanced sampling methods and assesses their druggability for potential inhibitor development.

Derlin rhomboid pseudoproteases employ substrate engagement and lipid distortion function for retrotranslocation of ER multi-spanning membrane substrates

This study identifies the mechanism by which derlin rhomboid pseudoproteases facilitate retrotranslocation of ER membrane substrates through substrate engagement and lipid thinning.

Structure and dynamics of SARS-CoV-2 proofreading exoribonuclease ExoN

This study determines the structure of SARS-CoV-2 ExoN and its interaction with nsp10, revealing mechanisms of RNA substrate binding and exoribonuclease activity.

Independent Markov Decomposition: Towards modeling kinetics of biomolecular complexes

This paper introduces Independent Markov Decomposition (IMD) to model kinetics of biomolecular complexes by decomposing systems into weakly coupled subsystems, reducing sampling requirements while preserving accuracy.

A glycan gate controls opening of the SARS-CoV-2 spike protein

This study identifies a glycan gate and key residues that facilitate SARS-CoV-2 spike protein RBD opening through simulations and experimental validation.

Discovery of an IKK2 Site that Allosterically Controls Its Activation

This paper identifies a novel allosteric site on IKK2 that can be targeted by small-molecule inhibitors to block its activity without ATP-competitive off-target effects.

SARS-CoV-2 escape in vitro from a highly neutralizing COVID-19 convalescent plasma

This study shows that three mutations in SARS-CoV-2 allowed it to escape neutralization by a highly neutralizing convalescent plasma.

Disease related mutations in PI3Kγ disrupt regulatory C-terminal dynamics and reveals a path to selective inhibitors

This study investigates how mutations in PI3Kγ affect its regulatory dynamics and identifies a strategy for developing selective inhibitors.

AI-Driven Multiscale Simulations Illuminate Mechanisms of SARS-CoV-2 Spike Dynamics

This paper develops an AI-driven workflow to simulate SARS-CoV-2 spike protein dynamics, revealing glycan shield structure, spike glycans' role in infectivity, and spike-ACE2 interactions.

Markov State Models and NMR Uncover an Overlooked Allosteric Loop in p53

The paper uses Markov state models and NMR to study p53 mutations, revealing a previously overlooked allosteric loop involved in conformational dynamics and mutation-induced inactivation.

A Multiscale Coarse-grained Model of the SARS-CoV-2 Virion

This paper develops a multiscale coarse-grained model of the SARS-CoV-2 virion using structural data and all-atom simulations to enable large-scale viral process simulations.

Benchmarking ensemble docking methods as a scientific outreach project

High school students benchmarked ensemble docking methods for ligand affinity prediction in a drug discovery challenge, finding Cathepsin S challenging and exploring advanced techniques.

The flexibility of ACE2 in the context of SARS-CoV-2 infection

This paper uses molecular dynamics simulations to study ACE2 flexibility in SARS-CoV-2 infection, finding structural dynamics that may aid viral entry and therapeutic design.

Multiscale simulations examining glycan shield effects on drug binding to influenza neuraminidase

This study uses multiscale simulations to show glycans reduce drug binding to influenza neuraminidase by sterically blocking the primary binding site.

Simulations support the interaction of the SARS-CoV-2 spike protein with nicotinic acetylcholine receptors

The paper uses molecular simulations to show that the SARS-CoV-2 spike protein's Y674-R685 loop binds to nicotinic acetylcholine receptors, with specific interactions and conformational changes observed across different receptor subtypes.

Beyond Shielding: The Roles of Glycans in SARS-CoV-2 Spike Protein

This study reveals the structural role of glycans in modulating SARS-CoV-2 spike protein conformational dynamics and ACE2 binding through molecular simulations and experiments.

An Open Source Mesh Generation Platform for Biophysical Modeling Using Realistic Cellular Geometries

The paper introduces GAMer 2, a mesh generation tool for converting structural biology data into geometric meshes suitable for biophysical modeling.

Active site plasticity and possible modes of chemical inhibition of the human DNA deaminase APOBEC3B

This study reports structures of APOBEC3B with loop 7 from APOBEC3G, revealing inactive conformations stabilized by small molecules, providing insights for inhibitor design.

Structural basis for ligand modulation of the CCR2 conformational landscape

This study investigates how orthosteric and allosteric antagonists affect CCR2 dynamics using molecular dynamics simulations and Markov-state models, revealing stable inactive conformations and potential drug binding sites.