Proteins in vacuo: Denaturing and folding mechanisms studied with computer-simulated molecular dynamics

✍ Scribed by Gustavo A. Arteca; C.T. Reimann; O. Tapia

• Publisher: John Wiley and Sons
• Year: 2001
• Tongue: English
• Weight: 346 KB
• Volume: 20
• Category: Article
• ISSN: 0277-7037
• DOI: 10.1002/mas.10012

✦ Synopsis

Abstract

| I. | Introduction | 402 |
| II. | Experiments and Simulations: Background | 403 |
| III. | Unfolding Studies | 406 |
| | A.  Centrifugal Unfolding of Neutral Proteins | 407 |
| | B.  Unfolding by Coulombic Repulsion | 409 |
| | C.  Unfolding by Screened van der Waals Attraction | 411 |
| IV. | Refolding Studies | 412 |
| V. | Closing Remarks | 414 |
| VI. | Acknowledgments | 415 |
| Appendix 1. Molecular Shape Descriptors for Protein Backbones | 416 |
| Appendix 2. MD Simulations | 417 |
| References | 419 |

Mounting evidence from experiments suggests that the native fold in solution is metastable in dehydrated proteins. Results from a number of experiments that use mass spectrometry indicate also that folding–unfolding transitions take place in protein ions even in the absence of water. These observations on anhydrous proteins call for a re‐evaluation of our understanding of the folding transition. In this context, computer‐assisted simulations are an important complementary tool. Here, we provide an overview of recent progress on the simulation of proteins in vacuo. In particular, we discuss the response of proteins and protein ions to perturbations that trigger unfolding and re‐folding transitions. By comparing the general patterns emerging from theory and experiment, we propose a series of new measurements that could help to validate, and improve, current simulation models. © 2002 Wiley Periodicals, Inc., Mass Spec Rev 20:402–422, 2001; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/mas.10012