ArticlePLoS computational biology2011
Multi-scaled explorations of binding-induced folding of intrinsically disordered protein inhibitor IA3 to its target enzyme.
Article in PLoS computational biology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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33 citing papers in PubMed, 72 citations in OpenAlex.
- Investigating the Conformational Dynamics of a Y-Family DNA Polymerase during Its Folding and Binding to DNA and a Nucleotide.JACS Au · 2022Article
- Molecular Simulations of Intrinsically Disordered Proteins and Their Binding Mechanisms.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Position-, disorder-, and salt-dependent diffusion in binding-coupled-folding of intrinsically disordered proteins.Physical chemistry chemical physics : PCCP · 2019Article
- Residual Structure Accelerates Binding of Intrinsically Disordered ACTR by Promoting Efficient Folding upon Encounter.Journal of molecular biology · 2019Article
- A Comprehensive Survey of the Roles of Highly Disordered Proteins in Type 2 Diabetes.International journal of molecular sciences · 2017Article
- Molecular mechanism of multispecific recognition of Calmodulin through conformational changes.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
- Role of non-native electrostatic interactions in the coupled folding and binding of PUMA with Mcl-1.PLoS computational biology · 2017Article
- Molecular dynamics simulation reveals how phosphorylation of tyrosine 26 of phosphoglycerate mutase 1 upregulates glycolysis and promotes tumor growth.Oncotarget · 2017Article
- Conformation Dynamics of the Intrinsically Disordered Protein c-Myb with theRSC advances · 2017Article
- Mapping transiently formed and sparsely populated conformations on a complex energy landscape.eLife · 2016Article
- Long range recognition and selection in IDPs: the interactions of the C-terminus of p53.Scientific reports · 2016Article
- Slow Internal Dynamics and Charge Expansion in the Disordered Protein CGRP: A Comparison with Amylin.Biophysical journal · 2015Article
- Identifying Similar Patterns of Structural Flexibility in Proteins by Disorder Prediction and Dynamic Programming.International journal of molecular sciences · 2015Article
- Article
- Dynamic conformational change regulates the protein-DNA recognition: an investigation on binding of a Y-family polymerase to its target DNA.PLoS computational biology · 2014Article
- Specificity and affinity quantification of flexible recognition from underlying energy landscape topography.PLoS computational biology · 2014Article
- Continuous wave W- and D-band EPR spectroscopy offer "sweet-spots" for characterizing conformational changes and dynamics in intrinsically disordered proteins.Biochemical and biophysical research communications · 2014Article
- Atomistic picture for the folding pathway of a hybrid-1 type human telomeric DNA G-quadruplex.PLoS computational biology · 2014Article
- Protein recognition and selection through conformational and mutually induced fit.Proceedings of the National Academy of Sciences of the United States of America · 2013Article
- Multiscaled exploration of coupled folding and binding of an intrinsically disordered molecular recognition element in measles virus nucleoprotein.Proceedings of the National Academy of Sciences of the United States of America · 2013Article
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Authors and funding
6 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Biomolecular function is realized by recognition, and increasing evidence shows that recognition is determined not only by structure but also by flexibility and dynamics. We explored a biomolecular recognition process that involves a major conformational change - protein folding. In particular, we explore the binding-induced folding of IA3, an intrinsically disordered protein that blocks the active site cleft of the yeast aspartic proteinase saccharopepsin (YPrA) by folding its own N-terminal residues into an amphipathic alpha helix. We developed a multi-scaled approach that explores the underlying mechanism by combining structure-based molecular dynamics simulations at the residue level with a stochastic path method at the atomic level. Both the free energy profile and the associated kinetic paths reveal a common scheme whereby IA3 binds to its target enzyme prior to folding itself into a helix. This theoretical result is consistent with recent time-resolved experiments. Furthermore, exploration of the detailed trajectories reveals the important roles of non-native interactions in the initial binding that occurs prior to IA3 folding. In contrast to the common view that non-native interactions contribute only to the roughness of landscapes and impede binding, the non-native interactions here facilitate binding by reducing significantly the entropic search space in the landscape. The information gained from multi-scaled simulations of the folding of this intrinsically disordered protein in the presence of its binding target may prove useful in the design of novel inhibitors of aspartic proteinases.
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