Shen Lab at Maryland
The Shen Group at U Maryland Pharmaceutical Sciences Explores
Structure-Dynamics-Function Relationships and Inhibition Strategies
We are a team of scientists from the University of Maryland's Pharmaceutical Sciences working at the intersection of chemistry, biology,
physics, medicine, and computer science. Our goal is to accelerate biomedical
discovery and materials innovation through the development and application of simulation and
data
science tools.
Email
Twitter @JanaShenLab
CpHMD
Drug Design
pK
Calculations
Membrane Proteins
Materials Design
Aiding the design of next-generation RAF inhibitors
Clayton et al, eLife, 2024
We discovered how dimer selectivity of BRAF inhibitors is linked to the remarkable allostery.
ML Models to Interrogate Proteomewide Covalent Ligandabilities
Ruibin Liu et al, JACS Au, 2024
We present a new database and ML models for predicting cysteine-ligandable hot spots in proteins.
Aarion won the Department of Pharmaceutical Sciences Merit Award!
Passion. Dedication. Hard work. Congratulations, Aarion! What a great start of the 4th year of PhD study!
Direct observation of chitin’s self assembly in silico
Romany et al, Chem Mater, 2023
De novo self assembly simulations of chitin revealed the mechanism of inverse temperature dependence and polymorphism.
Effective quantum descriptors for Michael acceptors
Liu et al, J Chem Inf Model, 2023
Low-cost quantum descriptors can predict the SAR of Michael acceptor warheads.
Towards covalently drugging the ERK pathway kinases
Romany et al, J Chem Inf Model, 2023
We identified druggable cysteines using a novel protocol that combines CpHMD and structural analysis.
Why is SARS-CoV-2 H172Y Mpro resistant to Paxlovid?
Clayton & Oliverira et al, JCIM, 2023
The drug resistance mechanism of a SARS-CoV-2 Mpro mutant revealed using simulations, AI, & experiments.
The GPU all-atom CpHMD is in Amber!
Julie Harris & Ruibin Liu, JCTC, 2022
We present the first CUDA implementation of the all-atom PME CpHMD method in Amber22.
Profiling MAPK cysteine reactivity in silico
Liu et al, RSC Med Chem, 2021
We assessed and rationalized the cysteine reactivities for all 14 MAP kinases.
Kinase front pocket cysteine has various reactivities
Liu & Zhan et al, J Med Chem, 2021
Exploring the reactivities of the front pocket cysteine in human kinases for covalent drug design.
How fentanyl unbinds from mu-opioid receptor
Mahinthichaichan et al, JACS Au 2021
We elucidated the mechanism and kinetics of fentanyl-mOR dissociation to help evaluate drug overdose reversal strategies.
Our first effort to combat the opioid crisis!
Vo et al, Nat Commun 2021
Deciphering how fentanyl binds mu-opioid receptor
represents the first step in understanding the cascade of
molecular events leading to addiction.
Towards
orally
available broad-spectrum
antiviral drugs
Verma et al, J Am Chem Soc 2020.
Study of SARS main proteases revealed
proton-coupled mechanism and an opportunity for small-molecule
broad-spectrum antiviral drug design
Address the
challenge of COVID-19 and beyond
Henderson et al, J Chem Phys, 2020
Studying proton-coupled conformational dynamics of a critical
enzyme
in SARS and MERS coronaviruses for broad-spectrum antiviral drug
design.
Nature’s backup plan for ion transporters
Henderson et al, Proc Natl Acad Sci 2020.
Alternative binding site and proton sharing may represent important
general mechanisms of proton-coupled transport in secondary active
transporters
Accurate prediction of reactive cysteines is
possible
Harris et al, J Chem Theory Comput 2020.
Benchmarking our GPU-based CpHMD tool to facilitate
targeted covalent inhibitor design
How does an electric field control soft
matter?
Mahinthichaichan et al, ACS Omega 2020.
Discover how electric signals induce conformational
changes of an aminopolysaccharide chain in an unexpected way
Persistence. Dedication. A true champion. Congrats to
Quynh Vo for completing the JPG puzzle challenge at
#bps20
pic.twitter.com/MfFlnsQ2aA
JGenPhysiol (@JGenPhysiol)
February
18, 2020
Electrostatic coupling enables conformational
plasticity of kinase
Tsai et al, J Am Chem Soc 2019.
Allowing protonation states to change may be a key
to sample the various conformational states of kinases.
Accelerating targeted covalent kinase
inhibitor design
Liu et al, J Am Chem Soc 2019.
A molecular dynamics tool put to test for
discovering covalent
hotspots in
kinases
and
other
drug targets.
Continuous constant pH molecular dynamics
released in Amber
Harris et al, J Chem Inf Model 2019.
A new GPU implementation for rapid and accurate
pK
predictions and
proton-coupled dynamics.
Modern materials: responsive, reconfigurable,
multi-functional
Tsai et al, Chem Mater 2018.
Exploiting a pK
gradient for persistent
but
erasable gradient
in
structural and mechanical properties.
Ligand protonation state controls water in
protein–ligand binding
Henderson et al, J Phys Chem Lett 2018.
Pyrimidine protonation shifts the ligand binding
mode from water-mediated to direct hydrogen bonding.