Biomedical subjects

Luonan Chen

Publications and source records attributed to Luonan Chen.

24 records · Page 2Linked to original sources

PubMed2005

Comparison of protein structures by multi-objective optimization.

We propose a novel method for solving the structure comparison problem for proteins, based on a decomposition technique. We define the structure alignment as a multi-objective optimization problem with both discrete and continuous variables, i.e., maximizing the number of aligned atoms and minimizing their root mean square distance. By controlling a single distance-related parameter, theoretically we can obtain a variety of optimal alignments corresponding to different optimal matching patterns, i.e., from a large matching portion to a small portion. The number of variables in our algorithm increases with the number of atoms of protein pairs in almost a linear manner. The software is available upon request, or from http://zhangroup.aporc.org/bioinfo/samo/.

Algorithms↗

PubMed2004

Protein structure alignment by deterministic annealing.

MOTIVATION: Protein structure alignment is one of the most important computational problems in molecular biology and plays a key role in protein structure prediction, fold family classification, motif finding, phylogenetic tree reconstruction and so on. From the viewpoint of computational complexity, a pairwise structure alignment is also a NP-hard problem, in contrast to the polynomial time algorithm for a pairwise sequence alignment. RESULTS: We propose a method for solving the structure alignment problem in an accurate manner at the amino acid level, based on a mean field annealing technique. We define the structure alignment as a mixed integer-programming (MIP) problem. By avoiding complicated combinatorial computation and exploiting the special structure of the continuous partial problem, we transform the MIP into a reduced non-linear continuous optimization problem (NCOP) with a much simpler form. To optimize the reduced NCOP, a mean field annealing procedure is adopted with a modified Potts model, whose solution is generally identical to that of the MIP. There is no 'soft constraint' in our mean field model and all constraints are automatically satisfied throughout the annealing process, thereby not only making the optimization more efficient but also eliminating many unnecessary parameters that depend on problems and usually require careful tuning. A number of benchmark examples are tested by the proposed method with comparisons to several existing approaches.

Algorithms↗

PubMed2004

Dynamics of gene regulatory networks with cell division cycle.

This paper focuses on modeling and analyzing the nonlinear dynamics of gene regulatory networks with the consideration of a cell division cycle with duplication process of DNA, in particular for switches and oscillators of synthetic networks. We derive two models that may correspond to the eukaryotic and prokaryotic cells, respectively. A biologically plausible three-gene model ( lac, tetR, and cI ) and a repressilator as switch and oscillator examples are used to illustrate our theoretical results. We show that the cell cycle may play a significant role in gene regulation due to the nonlinear dynamics of a gene regulatory network although gene expressions are usually tightly controlled by transcriptional factors.

Animals↗

PubMed2004

Intercellular communications induced by random fluctuations.

This paper investigates a general coupled noisy system for a cell-cell communication in a multi-cell system. The main conclusion is that appropriate noise intensity and coupling strength are capable of driving the coupled system to synchrony, which may be exploited by biological organisms to actively facilitate mutual communication. A multi-cell system with a synthetic gene network with both noises and delays is adopted to demonstrate the effect of noises on cellular communication.

Adaptation, Physiological↗

PubMed2003

Modeling genetic switches with positive feedback loops.

In this paper, we develop a new methodology to design synthetic genetic switch networks with multiple genes and time delays, by using monotone dynamical systems. We show that the networks with only positive feedback loops have no stable oscillation but stable equilibria whose stability is independent of the time delays. In other words, such systems have ideal properties for switch networks and can be designed without consideration of time delays, because the systems can be reduced from functional spaces to Euclidian spaces. Therefore, we can ensure that the designed switches function correctly even with uncertain delays. We first prove the basic properties of the genetic networks composed of only positive feedback loops, and then propose a procedure to design the switches, which drastically simplifies analysis of the switches and makes theoretical analysis and design tractable even for large-scaled systems. Finally, to demonstrate our theoretical results, we show biologically plausible examples by designing a synthetic genetic switch with experimentally well investigated lacI, tetR, and cI genes for numerical simulation.

Animals↗

PubMed2002

Design of genetic switches with only positive feedback loops.

We develop a new methodology to design synthetic genetic switch networks with multiple genes and time delays, by using monotone dynamical theory. We show that the networks with only positive feedback loops have no stable oscillation except equilibria whose stability is also independent of the time delays. Such systems have ideal properties for switch networks and can be designed with out consideration of time delays, because the systems can be reduced from functional spaces to Euclidian spaces due to the independence to time delays. Specifically, we first prove the basic properties of the genetic networks composed of only positive feedback loops, and then propose a procedure to design the switches, which drastically simplifies analysis of the switches and makes theoretical analysis and designing tractable even for large scale systems. Finally, we demonstrate our theoretical results by designing a biologically plausible synthesized genetic switch with experimentally well investigated lacI, tetR, and cI genes.

Adaptation, Physiological↗