Protein folding

Protein folding
Name	Protein folding
Field	Biochemistry
Known for	Studies of three-dimensional structure of polypeptides

Protein folding Protein folding is the process by which a polypeptide chain acquires its functional three-dimensional structure through intramolecular interactions and interactions with the environment. Research on this topic spans laboratories, universities, and institutions across the world and intersects with work by notable figures and organizations in chemistry, biology, and physics. Major experimental, computational, and theoretical advances have been driven by collaborations among groups at Harvard University, Stanford University, Massachusetts Institute of Technology, University of Cambridge, and industrial research centers like Genentech and Pfizer.

Introduction

Foundational studies emerged from laboratories associated with Max Perutz and John Kendrew at the Cavendish Laboratory and researchers at Rockefeller University and Columbia University. Central concepts were formalized through influence from investigators at the National Institutes of Health and awards such as the Nobel Prize in Chemistry. Early structural determination by teams at European Molecular Biology Laboratory and MRC Laboratory of Molecular Biology established paradigms later elaborated by groups at California Institute of Technology and ETH Zurich.

Mechanisms and Pathways

Models for folding pathways were developed in research programs at Princeton University and University of California, Berkeley and refined through collaborations with scientists at University of Oxford and Tokyo University. The energy landscape theory drew on contributions from investigators at IBM Research and from theoreticians affiliated with CNRS and Max Planck Society. Kinetic folding intermediates were characterized in laboratories at Johns Hopkins University, Scripps Research, and University of Michigan while chaperone-mediated routes were elucidated by teams at University of Geneva and Rockefeller University.

Experimental Methods

Techniques central to structural and kinetic analysis were advanced at facilities like Brookhaven National Laboratory and Lawrence Berkeley National Laboratory; high-resolution methods emerged from groups at European Synchrotron Radiation Facility and Diamond Light Source. Nuclear magnetic resonance developments trace to work at Institut Laue–Langevin and Bruker collaborations with academia. Single-molecule methods were advanced by investigators at Columbia University, Stanford University Medical Center, and University of Illinois Urbana-Champaign; cryo-electron microscopy breakthroughs involved teams at EMBL and instrument developers at Thermo Fisher Scientific.

Computational Models and Prediction

Computational prediction advanced through projects at DeepMind, University of Washington, and University of California, San Francisco with contributions from research groups at Argonne National Laboratory and Los Alamos National Laboratory. Molecular dynamics simulations were driven by software from D. E. Shaw Research and research at Riken and Purdue University. Algorithms combining physics-based and machine learning approaches received support through collaborations with Google and initiatives at European Bioinformatics Institute and National Center for Biotechnology Information.

Biological Significance and Diseases

Links between misfolding and disease were established through clinical and basic research at Mayo Clinic, Johns Hopkins Hospital, and Rettberg Institute; prion research involved groups at University of Edinburgh and Prionics. Studies connecting folding defects to neurodegeneration relied on collaborations with teams at Massachusetts General Hospital and Karolinska Institutet. Pharmaceutical development targeting folding pathways included programs at Novartis, GlaxoSmithKline, and AstraZeneca; translational work has engaged consortia supported by Wellcome Trust and Bill & Melinda Gates Foundation.

Folding in the Cellular Context

Cellular folding studies were advanced by labs at Max Planck Institute for Biophysical Chemistry, Heidelberg University, and UCSF Medical Center examining ribosome-associated folding and co-translational mechanisms characterized by researchers at Weizmann Institute of Science and University of Copenhagen. Quality control and degradation pathways were dissected by teams at Cold Spring Harbor Laboratory and European Molecular Biology Laboratory. Interactions with membranes and organelles were examined in collaborations involving Stanford University School of Medicine and Yale University.

Historical Development and Key Concepts

Historical milestones trace through archives and laboratories at Cambridge University Press publishing early monographs, through conferences hosted by Gordon Research Conferences and Cold Spring Harbor Laboratory symposia, and through awards including the Lasker Award. Seminal hypotheses and experiments originated in the period involving researchers associated with Royal Society meetings and were shaped by theoretical work at institutions like Princeton Plasma Physics Laboratory and Imperial College London. Modern trajectories continue through interdisciplinary centers at University of Tokyo and Seoul National University integrating structural biology, biophysics, and computational science.

Category:Molecular biology