Application of artificial intelligence and machine learning techniques to the analysis of dynamic protein sequences.

We apply methods of Artificial Intelligence and Machine Learning to protein dynamic bioinformatics. We rewrite the sequences of a large protein data set, containing both folded and intrinsically disordered molecules, using a representation developed previously, which encodes the intrinsic dynamic properties of the naturally occurring amino acids. We Fourier analyze the resulting sequences.

Global Survey of Protein Dynamic Properties.

Using tools developed to study the dynamic bioinformatics of proteins, we are able to study the dynamic characteristics of very large numbers of protein sequences simultaneously. We study herein the distribution of protein sequences in a space determined by sequence mobility. It is shown that there are statistically significant differences in mobility distribution between folded sequences of different structural classes and between those and sequences of intrinsically disordered proteins.

The dynamic basis of structural order in proteins.

We compare the sequences of folded and intrinsically disordered proteins (IDPs), using bioinformatic methods recently developed to study protein dynamic properties. We demonstrate that the two classes of sequences are organized in diametrically opposite ways with respect to long-length-scale dynamic properties. We further demonstrate a statistically significant difference between the amino acid compositions of folded and disordered proteins, which is expressed in dynamic properties.

X-Ray fluorescence microscopy reveals that rhenium(i) tricarbonyl isonitrile complexes remain intact in vitro.

The complex fac-[Re(CO)3(dmphen)(para-tolylisonitrile)]+ (TRIP), where dmphen = 2,9-dimethyl-1,10-phenanthroline, is an endoplasmic reticulum stress-inducing anticancer agent (A. P. King, S.

Systematically altering the lipophilicity of rhenium(I) tricarbonyl anticancer agents to tune the rate at which they induce cell death.

Rhenium-based anticancer agents have arisen as promising alternatives to conventional platinum-based drugs. Based on previous studies demonstrating how increasing lipophilicity improves drug uptake within the cell, we sought to investigate the effects of lipophilicity on the anticancer activity of a series of six rhenium(i) tricarbonyl complexes. These six rhenium(i) tricarbonyl structures, called Re-Chains, bear pyridyl imine ligands with different alkyl chains ranging in length from two to twelve carbons.

In Vivo Anticancer Activity of a Rhenium(I) Tricarbonyl Complex.

The rhenium(I) complex -[Re(CO)(2,9-dimethyl-1,10-phenanthroline)(OH)] () was previously shown to exhibit potent in vitro anticancer activity in a manner distinct from conventional platinum-based drugs ( , , 14302-14314). In this study, we report further efforts to explore its aqueous speciation and antitumor activity. The cellular uptake of was measured in A2780 and cisplatin-resistant A2780CP70 ovarian cancer cells by inductively coupled plasma mass spectrometry, revealing similar uptake efficiency in both cell lines.

Combinatorial Synthesis to Identify a Potent, Necrosis-Inducing Rhenium Anticancer Agent.

Combinatorial synthesis can be applied for developing a library of compounds that can be rapidly screened for biological activity. Here, we report the application of microwave-assisted combinatorial chemistry for the synthesis of 80 rhenium(I) tricarbonyl complexes bearing diimine ligands. This library was evaluated for anticancer activity in three different cancer cell lines, enabling the identification of three lead compounds with cancer cell growth-inhibitory activities of less than 10 μM.

Anticancer activity of complexes of the third row transition metals, rhenium, osmium, and iridium.

The clinical success of the platinum-based chemotherapeutic agents has prompted the investigation of coordination and organometallic complexes of alternative metal centers for use as anticancer agents. Among these alternatives, the third row transition metal neighbors of platinum on the periodic table have only recently been explored for their potential to yield anticancer-active complexes. In this Perspective, we summarize developments within the last six years on the application of rhenium, osmium, and iridium complexes as anticancer drug candidates.