Dylan Jayatilaka

• The University of Western Australia

What molecular formulae correspond to a given mass M? Here, we address this problem - the compomer problem of mass spectrometry. We describe, implement, and test a straightforward and practical aufbau algorithm which leads to the molecular formula tree from which all possible solutions may be obtained. The algorithm was inspired from the generating...

Supporting text (Text S1) is available giving further information on the nature of the model binding sites, and additional results showing the free energy values for both forward and reverse FEP morphs. (PDF)

Several mechanisms have been proposed to explain how ion channels and transporters distinguish between similar ions, a process crucial for maintaining proper cell function. Of these, three can be broadly classed as mechanisms involving specific positional constraints on the ion coordinating ligands which arise through: a "rigid cavity", a 'strained...

Some biological molecules can distinguish between ions of similar nature, which may be achieved by enforcing specific coordination numbers on ions in the binding site. It is suggested that when this number is favourable for one ion type, but too large for another, this creates ion selectivity through the proposed mechanism of 'overcoordination'. Mu...

A novel refinement technique for X-ray diffraction data has been employed to derive SO bond orders in sulfur dioxide experimentally. The results show that ionic SO bonding dominates over hypervalency.

Open pore structure of MscL from a coarse grained simulation using distance and solvent restraints combined with membrane tension ( (1)) showing a pore radius of 13.7 Å. Each residue is represented by a backbone particle and 0 or more side chain particles. Open pore structure of MscL from a coarse grained simulation using distance and solvent restr...

The supplementary material contains additional analysis of the distance restraints (Figure S1), supporting Figures for the structural analysis of the potential open pore structures (S2 to S4) as well as additional data for the analysis of the kink in TM1 (Figure S5) and the simulations of MscL in short-chain lipids (Figure S6 and S7). It also conta...

Author Summary Cells in biological organisms have to be able to respond to mechanical forces during processes such as touch, hearing, pain sensation and tissue growth. One way this is achieved is through mechanosensitive ion channels, membrane embedded proteins that initiate electrical signalling upon tension within the cell or cell membrane. The m...

Mechanosensitive channels are ubiquitous membrane proteins where gating is induced by tension in the lipid bilayer. A high resolution structure of the closed pore of the mechanosensitive channel of large conductance (MscL) is known and the protein has been characterized in different functional states using EPR [1] and FRET [2] spectroscopy. However...

Fluorescence resonance energy transfer (FRET) can be utilized to gain low-resolution structural information by reporting on the proximity of molecules or measuring inter- and intramolecular distances. This method exploits the fact that the probability of the energy transfer is related to the separation between the fluorescent molecules. This relati...

The crystal structure of the β-polymorph of hydroquinone (β-HQ), the apohost of a large family of clathrates, is reported with a specific focus on intermolecular interactions and the electrostatic nature of its cavity. Hirshfeld surface analysis reveals subtle close contacts between two interconnecting HQ networks, and the local packing and related...

It is still a challenge to predict a compound's reactivity from its ground-state electronic nature although Bader-type topological analyses of the electron density (ED) and electron localizability indicator (ELI) give detailed and useful information on electron concentration and electron-pair localization, respectively. Both ED and ELI can be obtai...

Fluorescence resonance energy transfer (FRET) is commonly used to determine the proximity of fluorophores, but usually many assumptions are required to gain a quantitative relationship between the likelihood of energy transfer and fluorophore separation. Molecular Dynamics (MD) simulations provide one way of checking these assumptions, but before u...

We present a simple and more realistic alternative to the conventional approach of mapping void space by rolling a probe sphere of variable radius over a fused-sphere representation of a molecular crystal. Based on isosurfaces of the procrystal electron density, this approach can be used to locate and visualise the void space in crystalline materia...

The ability of macrocycles, enzymes, ion channels, transporters, and DNA to differentiate among ion types is often crucial to their function. Using molecular dynamics simulations on both detailed systems and simple models, we quantify the importance of several factors which affect the ion selectivity of such molecules, including the number of coord...

No longer hidden! An extension of the capabilities of the X-ray diffraction experiment is introduced. Locations of electron pairs within a molecule can be measured and made visible (see figure). This is demonstrated on a series of epoxides, for which ring strain, crystal, and substituent effects can be quantified. Comparison with experimental and t...

The aspartate transporter GltPH is an integral membrane protein that catalyses the movement of aspartate across lipid bilayers. GltPH utilises established ion gradients, transporting two sodium ions with each aspartate molecule. Previous studies have shown that the ion binding sites demonstrate selectivity for Na+ over both Li+ and K+ (Na+ > Li+ >...

Fluorescence resonance energy transfer (FRET) can be utilized to gain low resolution structural information, making use of the fact that the probability of energy transfer is related to the distances between fluorescent molecules. Although the relationship between the efficiency of energy transfer and the distance between sites is well described fo...

Fluorescence Resonance Energy Transfer (FRET) spectroscopy is a technique that is widely used to obtain co-localization and structural information of proteins in their native environment. The technique is based on the mechanism of energy transfer by dipole-dipole induced, non-radiative interaction between a fluorescent donor and a suitable acceptor...

Refractive indices for molecular crystals are obtained from Hartree-Fock wavefunctions constrained to reproduce a set of experimental X-ray structure factors. Coupled-perturbed Hartree-Fock theory is used to calculate the in-crystal effective polarizabilities from which the refractive indices are obtained, thus eliminating the need for the calibrat...

Numerous biological molecules selectively bind or transport particular ions. In biological systems, the discrimination between sodium and potassium is particularly important. We demonstrate that selectivity of group I ions is dependent on three factors; the dipole moment of the coordinating ligands [1], the number of coordinating ligands [2] and th...

In the last few years the analysis of molecular crystal structures using tools based on Hirshfeld surfaces has rapidly gained in popularity. This approach represents an attempt to venture beyond the current paradigm—internuclear distances and angles, crystal packing diagrams with molecules represented via various models, and the identification of c...

Measurements of time-resolved fluorescence anisotropy and fluorescence resonance energy transfer are finding many applications in the study of biological macromolecules as they enable structural properties of the host molecules to be determined in their natural environment. A difficulty in interpreting these experiments is that they both require kn...

Ab initio electrostatic potentials for molecules can readily be mapped onto their Hirshfeld surfaces and displayed within a crystal packing diagram. In this manner the close molecular contacts in the crystal can be rationalized and discussed in terms of the electrostatic complementarity of touching surface patches in adjacent molecules. By way of e...

Enhancements to the properties based on Hirshfeld surfaces enable quantitative comparisons between contributions to crystal packing from various types of intermolecular contacts.

Potassium channels are exquisitely selective, allowing K+ to pass across cell membranes while blocking other ion types. Here we demonstrate that the number of carbonyl oxygen atoms that surround permeating ions is the most important factor in determining ion selectivity rather than the size of the pore or the strength of the coordinating dipoles. A...

We describe the use of dipole lattice sums to estimate the electric field experienced by a molecule in a crystal, and apply it iteratively to ab initio calculations on a number of molecules of interest for nonlinear optical applications. The results demonstrate that it represents an efficient and reliable route to estimating molecular dipole moment...

Although it was proposed some time ago that (hyper)polarizabilities might be estimated from the results of x-ray charge density refinements, early results were unconvincing. In this work we show that the one particle density obtained from the usual multipole refinement model does not contain sufficient information to determine these response proper...

Orientational fluorophores have been a useful tool in physical chemistry, biochemistry, and more recently structural biology due to the polarized nature of the light they emit and that fact that energy can be transferred between them. We present a practical scheme in which measurements of the intensity of emitted fluorescence can be used to determi...

We describe a procedure to extract a single determinant wave function from x-ray charge density structure factors. The orbitals obtained can be seen as Hartree-Fock orbitals constrained to give the experimental density to a prescribed accuracy. The method is applied to beryllium metal. From our wave function we extract the binding energy and work f...

Resonance energy transfer provides a practical way to measure distances in the range of 10-100 A between sites in biological molecules. Although the relationship between the efficiency of energy transfer and the distance between sites is well described for a single pair of fluorophores, the situation is more difficult when more than two fluorophore...