Biomedical subjects

Jesper Ferkinghoff-Borg

Publications and source records attributed to Jesper Ferkinghoff-Borg.

7 recordsLinked to original sources

PubMed2005

Diffusion, fragmentation, and coagulation processes: analytical and numerical results.

We formulate dynamical rate equations for physical processes driven by a combination of diffusive growth, size fragmentation, and fragment coagulation. Initially, we consider processes where coagulation is absent. In this case we solve the rate equation exactly leading to size distributions of Bessel type which fall off as exp(-x(3/2)) for large x values. Moreover, we provide explicit formulas for the expansion coefficients in terms of Airy functions. Introducing the coagulation term, the full nonlinear model is mapped exactly onto a Riccati equation that enables us to derive various asymptotic solutions for the distribution function. In particular, we find a standard exponential decay exp(-x) for large x and observe a crossover from the Bessel function for intermediate values of x . These findings are checked by numerical simulations, and we find perfect agreement between the theoretical predictions and numerical results.

Journal Article↗

PubMed2005

Novel optical and statistical methods reveal colloid-wall interactions inconsistent with DLVO and Lifshitz theories.

We present an experimental method based on video microscopy to perform nanometer scale position detection of a micrometer bead in the direction along the propagation of the detection light. Using the same bead for calibration and detection significantly improves the in depth resolution in comparison to video microscopy methods from literature. This method is used together with an optical trap to measure interaction potentials between a glass surface and colloids made of polystyrene or silica at different electrolyte concentrations. The results are confirmed by an independent method where the optical trap is used in connection with a quadrant photodiode. Also, we present a maximum likelihood analysis method which considerably improves the spatial resolution of interaction potentials by optimizing the underlying potential function to fit all observed position distributions. The measured interaction potentials agree well with DLVO theory for small electrolyte concentrations; however, for larger electrolyte concentrations the potentials differ qualitatively from both DLVO and Lifshitz theory.

Journal Article↗

PubMed2005

Prediction of water and metal binding sites and their affinities by using the Fold-X force field.

The empirical force field Fold-X was developed previously to allow rapid free energy calculations in proteins. Here, we present an enhanced version of the force field allowing prediction of the position of structural water molecules and metal ions, together called single atom ligands. Fold-X picks up 76% of water molecules found to interact with two or more polar atoms of proteins in high-resolution crystal structures and predicts their position to within 0.8 A on average. The prediction of metal ion-binding sites have success rates between 90% and 97% depending on the metal, with an overall standard deviation on the position of binding of 0.3-0.6 A. The following metals were included in the force field: Mg2+, Ca2+, Zn2+, Mn2+, and Cu2+. As a result, the current version of Fold-X can accurately decorate a protein structure with biologically important ions and water molecules. Additionally, the free energy of binding of Ca2+ and Zn2+ (i.e., the natural logarithm of the dissociation constant) and its dependence on ionic strength correlate reasonably well with the experimental data available in the literature, allowing one to discriminate between high- and low-affinity binding sites. Importantly, the accuracy of the energy prediction presented here is sufficient to efficiently discriminate between Mg2+, Ca2+, and Zn2+ binding.

Biophysics↗

PubMed2005

Recognizing and defining true Ras binding domains II: in silico prediction based on homology modelling and energy calculations.

Considering the large number of putative Ras effector proteins, it is highly desirable to develop computational methods to be able to identify true Ras binding molecules. Based on a limited sequence homology among members of the Ras association (RA) and Ras binding (RB) sub-domain families of the ubiquitin super-family, we have built structural homology models of Ras proteins in complex with different RA and RB domains, using the FOLD-X software. A critical step in our approach is to use different templates of Ras complexes, in order to account for the structural variation among the RA and RB domains. The homology models are validated by predicting the effect of mutating hot spot residues in the interface, and residues important for the specificity of interaction with different Ras proteins. The FOLD-X calculated energies of the best-modelled complexes are in good agreement with previously published experimental data and with new data reported here. Based on these results, we can establish energy thresholds above, or below which, we can predict with 96% confidence that a RA/RB domain will or will not interact with Ras. This study shows the importance of in depth structural analysis, high quality force-fields and modelling for correct prediction. Our work opens the possibility of genome-wide prediction for this protein family and for others, where there is enough structural information.

Amino Acid Sequence↗

PubMed2005

SNPeffect: a database mapping molecular phenotypic effects of human non-synonymous coding SNPs.

Single nucleotide polymorphisms (SNPs) are an increasingly important tool for genetic and biomedical research. However, the accumulated sequence information on allelic variation is not matched by an understanding of the effect of SNPs on the functional attributes or 'molecular phenotype' of a protein. Towards this aim we developed SNPeffect, an online resource of human non-synonymous coding SNPs (nsSNPs) mapping phenotypic effects of allelic variation in human genes. SNPeffect contains 31 659 nsSNPs from 12 480 human proteins. The current release of SNPeffect incorporates data on protein stability, integrity of functional sites, protein phosphorylation and glycosylation, subcellular localization, protein turnover rates, protein aggregation, amyloidosis and chaperone interaction. The SNP entries are accessible through both a search and browse interface and are linked to most major biological databases. The data can be displayed as detailed descriptions of individual SNPs or as an overview of all SNPs for a given protein. SNPeffect will be regularly updated and can be accessed at http://snpeffect.vib.be/.

Alleles↗

PubMed2003

Competition between diffusion and fragmentation: an important evolutionary process of nature.

We investigate systems of nature where the common physical processes diffusion and fragmentation compete. We derive a rate equation for the size distribution of fragments. The equation leads to a third order differential equation which we solve exactly in terms of Bessel functions. The stationary state is a universal Bessel distribution described by one parameter, which fits perfectly experimental data from two very different systems of nature, namely, the distribution of ice-crystal sizes from the Greenland ice sheet and the length distribution of alpha helices in proteins.

Crystallization↗

PubMed2003

Compact phases of polymers with hydrogen bonding.

We propose an off-lattice model for a self-avoiding homopolymer chain with two different competing attractive interactions, mimicking the hydrophobic effect and the hydrogen-bond formation, respectively. By means of Monte Carlo simulations, we are able to trace out the complete phase diagram for different values of the relative strengths of the two competing interactions. For strong enough hydrogen bonding, the ground state is a helical conformation, whereas with decreasing hydrogen-bonding strength, helices get eventually destabilized at low temperature in favor of more compact conformations resembling beta sheets appearing in the native structures of proteins. For weaker hydrogen bonding helices are not thermodynamically relevant anymore.

Journal Article↗