John E. Straub

About

Professor John E. Straub is a faculty member at Boston University, where he leads the Straub Lab. His research group focuses on the biophysical and computational study of amyloid proteins and their aggregation processes. The lab investigates the structure, stability, and formation mechanisms of amyloid fibrils, including those formed by Serum Amyloid A protein and amyloid-beta peptides. Research in the group also explores the role of hydration, polyanions, and membrane interactions in amyloid formation and protein-protein association. The lab employs a range of modeling approaches, from all-atom simulations to coarse-grained and lattice models, to understand the thermodynamics and kinetics underlying protein aggregation and phase separation in lipid mixtures. Professor Straub's group also develops algorithms to elucidate optimal transition pathways and studies the effects of membrane friction on molecular isomerization, contributing to the understanding of tension-based probes in biophysical systems.

Research topics

• Computer Science
• Chemistry
• Artificial Intelligence
• Neuroscience
• Computational chemistry
• Molecular physics
• Chemical physics
• Organic chemistry
• Pathology
• Biology

Selected publications

• Amyloid Oligomers: A Joint Experimental/Computational Perspective on Alzheimer’s Disease, Parkinson’s Disease, Type II Diabetes, and Amyotrophic Lateral Sclerosis

  Chemical Reviews · 2021 · 653 citations

  , and pharmacological experiments tell us about the accumulation and deposition of the oligomers of the (Aβ, tau), α-synuclein, IAPP, and superoxide dismutase 1 proteins, which have been the mainstream concept underlying Alzheimer's disease (AD), Parkinson's disease (PD), type II diabetes (T2D), and amyotrophic lateral sclerosis (ALS) research, respectively, for many years.

  DOI

• Vibrational Spectroscopic Map, Vibrational Spectroscopy, and Intermolecular Interaction

  Chemical Reviews · 2020 · 396 citations

  Vibrational spectroscopy is an essential tool in chemical analyses, biological assays, and studies of functional materials. Over the past decade, various coherent nonlinear vibrational spectroscopic techniques have been developed and enabled researchers to study time-correlations of the fluctuating frequencies that are directly related to solute-solvent dynamics, dynamical changes in molecular conformations and local electrostatic environments, chemical and biochemical reactions, protein structu…

  PublisherOA PDFDOI

• Differences in the free energies between the excited states of A <i>β</i> 40 and A <i>β</i> 42 monomers encode their aggregation propensities

  Proceedings of the National Academy of Sciences · 2020 · 72 citations

  The early events in the aggregation of the intrinsically disordered peptide, amyloid-β (Aβ), involve transitions from the disordered free energy ground state to assembly-competent states. Are the fingerprints of order found in the amyloid fibrils encoded in the conformations that the monomers access at equilibrium? If so, could the enhanced aggregation rate of Aβ42 compared to Aβ40 be rationalized from the sparsely populated high free energy states of the monomers? Here, we answer these question…

  DOI

• Cholesterol and Lipid Rafts in the Biogenesis of Amyloid-β Protein and Alzheimer's Disease

  Annual Review of Biophysics · 2024-02-21 · 28 citations

  reviewOpen accessSenior author

  Cholesterol has been conjectured to be a modulator of the amyloid cascade, the mechanism that produces the amyloid-β (Aβ) peptides implicated in the onset of Alzheimer's disease. We propose that cholesterol impacts the genesis of Aβ not through direct interaction with proteins in the bilayer, but indirectly by inducing the liquid-ordered phase and accompanying liquid-liquid phase separations, which partition proteins in the amyloid cascade to different lipid domains and ultimately to different e…

  PublisherDOI

• Machine Learning Derived Collective Variables for the Study of Protein Homodimerization in Membrane

  Journal of Chemical Theory and Computation · 2024-06-25 · 15 citations

  articleOpen accessSenior authorCorresponding

  The accurate calculation of equilibrium constants for protein-protein association is of fundamental importance to quantitative biology and remains an outstanding challenge for computational biophysics. Traditionally, equilibrium constants have been computed from one-dimensional free energy surfaces derived from sampling along a single collective variable. Importantly, recent advances in enhanced sampling methodology have facilitated the characterization of multidimensional free energy landscapes…

  PublisherOA PDFDOI

Recent grants

• Algorithms for the simulation of strong phase changes in complex molecular systems

  NSF · $500k · 2011–2015

• Algorithms for enhanced sampling and global optimization

  NSF · $372k · 1999–2003

• NIH Grant R01NS041356

  NIH · $1.1M · 2005

Frequent coauthors

• D. Thirumalai

  90 shared

• Hiroshi Fujisaki

  Nippon Medical School

  34 shared

• George A. Pantelopulos

  National Institutes of Health

  32 shared

• Diane E. Sagnella

  28 shared

• Timothy A. Jackson

  University of Kansas

  25 shared

• Manho Lim

  Pusan National University

  25 shared

• Philip Anfinrud

  National Institute of Diabetes and Digestive and Kidney Diseases

  25 shared

• Bogdan Tarus

  Université Paris-Saclay

  22 shared

Labs

• Straub LabPI

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• Tom Tulliush-57
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