We present an all atom potential energy function for the simulation of proteins and nucleic acids. This work is an extension of the CH united atom function recently presented by S.J. Weiner et al. J. Amer. Chem. Soc., 106, 765 (1984). The parameters of our function are based on calculations on ethane, propane, n−butane, dimethyl ether, methyl ethyl ether, tetrahydrofuran, imidazole, indole, deoxyadenosine, base paired dinucleoside phosphates, adenine, guanine, uracil, cytosine, thymine, insulin, and myoglobin. We have also used these parameters to carry out the first general vibrational analysis of all five nucleic acid bases with a molecular mechanics potential approach.

An all atom force field for simulations of proteins and nucleic acids.

Recent experiments, advances in theory, and analogies to other complex systems such as glasses and spin glasses yield insight into protein dynamics. The basis of the understanding is the observation that the energy landscape is complex: Proteins can assume a large number of nearly isoenergetic conformations (conformational substates). The concepts that emerge from studies of the conformational substates and the motions between them permit a quantitative discussion of one simple reaction, the binding of small ligands such as carbon monoxide to myoglobin.

https://science.sciencemag.org/content/sci/254/5038/1598.full.pdf

The energy landscapes and motions of proteins.

Molecular dynamics simulations are important tools for understanding the physical basis of the structure and function of biological macromolecules. The early view of proteins as relatively rigid structures has been replaced by a dynamic model in which the internal motions and resulting conformational changes play an essential role in their function. This review presents a brief description of the origin and early uses of biomolecular simulations. It then outlines some recent studies that illustrate the utility of such simulations and closes with a discussion of their ever-increasing potential for contributing to biology.

Molecular dynamics simulations of biomolecules

Because proteins are central to cellular function, researchers have sought to uncover the secrets of how these complex macromolecules execute such a fascinating variety of functions. Although static structures are known for many proteins, the functions of proteins are governed ultimately by their dynamic character (or 'personality'). The dream is to 'watch' proteins in action in real time at atomic resolution. This requires addition of a fourth dimension, time, to structural biology so that the positions in space and time of all atoms in a protein can be described in detail.

http://www.ifm.liu.se/edu/coursescms/TFKE40/literature/KernD_Nature07_Review.pdf

Dynamic personalities of proteins.

Fluorescence quenching studies with proteins.

X-ray diffraction at four temperatures from 220 to 300 K coupled with crystallographic refinement yields the mean-square displacements and conformational potentials of all 1,261 non-hydrogen atoms of metmyoglobin. The results are interpreted to indicate a condensed core around the haem, semi-liquid regions towards the outside and a possible pathway for ligands. It is concluded that X-ray diffraction can provide the spatial distribution of the dynamic features of a protein.

Temperature-dependent X-ray diffraction as a probe of protein structural dynamics

https://febs.onlinelibrary.wiley.com/doi/pdf/10.1016/0014-5793%2876%2980390-0

The crystal structure of a post-synaptic neurotoxin from sea snake at 2.2 Å resolution

Structure of oxidized flavodoxin from Anacystis nidulans

The structure of a specific acyl-enzyme intermediate in the elastase-catalysed hydrolysis of N-carbobenzoxy-L-alanyl-p-nitrophenol ester has been determined by X-ray diffraction at 3.5 A resolution. The acyl-enzyme was stabilised by cooling the crystal to −55°C during substrate addition and data collection.

Crystal structure of elastase-substrate complex at -55 °C

A hydrogen-bonded ion pair between the guanidinium group of the arginine at position 37 and the side-chain carboxylate of the aspartic acid residue at position 31 of sea snake venom neurotoxin has stereochemical features resembling those of acetylcholine. The results of crystallographic determination of the structure of the neurotoxin suggest that such an ion pair can form at the tip of the "toxic loop" and may be involved in inhibition of the cholinergic receptor.

Demetrius Tsernoglou

Papers

Temperature-dependent X-ray diffraction as a probe of protein structural dynamics

The crystal structure of a post-synaptic neurotoxin from sea snake at 2.2 Å resolution

Structure of oxidized flavodoxin from Anacystis nidulans

Crystal structure of elastase-substrate complex at -55 °C

Structure and Function of Snake Venom Curarimimetic Neurotoxins