Sequences physicochemical properties based

One of the main motivations of using synthetic DNA for cellular engineering seems to be at odds with the random nature of directed evolution. Traditionally, PCR-based methods have been used to create sequence diversity, inspired by the fact that mutations in nature commonly arise from errors in DNA replication. PCR-based methods are preferred when there is no prior knowledge about where mutations are likely to influence the traits of interest, but are limited in that the sequence diversity that results is restricted and biased. With single base mutations per codon - a common assumption with most protocols - only 5.7 amino acids are accessible per position on average, and in most cases, the resulting set of amino acids does not accurately represent the spectrum of physicochemical properties of naturally-occurring residues [76]. 

Noteworthy in this perspective is the recent work done at Pfizer and Biofocus (see Section 5.5), where, based on analysis of sequence data, mutation data, and physicochemical properties of the ligands, approaches were outlined for discovering sequence patterns characteristic of specific ligand classes. Pfizer applied the approach successfully to the construction of a sequence motif characteristic of monoamine GPCRs [74],... 

Gasteiger et al. returned to the initial I s) curve and maintained the explicit form of the curve [36]. For A they substituted various physicochemical properties such as atomic mass, partial atomic charges, and atomic polarizability. To obtain uniform length descriptors, the intensity distribution I s) is made discrete, calculating its value at a sequence of evenly distributed values of, for example, 32 or 64 values in the range of 0 - 3lA. The resolution of the molecule representation increases with higher number of values. The resulting descriptor is the 3D MoRSE (Molecular Representation of Structures based on Electron diffraction) Code. 

PAM matrix PAM (percent accepted mutation) and BLOSUM (blocks substitution matrix) are matrices that define scores for each of the 210 possible amino acid substitutions. The scores are based on empirical substitution frequencies observed in alignments of database sequences and in general reflect similar physicochemical properties (e.g., a substitiution of leucine for isoleucine, two amino acids of similar hydrophobicity and size, will score higher than a substitution of leucine for glutamate.)... 

To synthesize polynucleotide analogues closely resembling natural polymers, we have synthesized several new monomers such as dihydrofuran and dihydropyran derivatives which contained nucleic acid bases (Scheme 1). Copolymerization of the monomers either with maleic anhydride or with vinylene carbonate resulted in the alternating copolymers as shown in Scheme 2. Hydrolysis of the products gave the polymers which were optically active and soluble in water and had alternating sequences along the polymer chain. In this paper we will report synthesis of monomers, their copolymerization either with maleic anhydride or with vinylene carbonate, hydrolysis of the copolymers, and the physicochemical properties of the anhydride and hydrolyzed polymers. 

Abstract Chemical structure, polymer microstructme, sequence distribution, and morphology of acid-bearing polymers are important factors in the design of polymer electrolyte membranes (PEMs) for fuel cells. The roles of ion aggregation and phase separation in vinylic- and aromatic-based polymers in proton conductivity and water transport are described. The formation, dimensions, and connectivity of ionic pathways are consistently found to play an important role in determining the physicochemical properties of PEMs. For polymers that possess low water content, phase separation and ionic channel formation significantly enhance the transport of water and protons. For membranes that contain a high... 

Based on the existence of type-II p-tums within short resilin sequences (Table 1), similar p-stmctures have also been invoked in the dastic mechanism of resilin (although energetic differences may exist between the dastic recoil mechanisms of the two protdns based on their different physicochemical properties). Ldj et proposed a modd invoking nonre-... 

Mutagens can be divided into two main types—chemical and physical—both of which act on the DNA molecule. Chemical mutagens induce mutation in two ways first, the combination of the mutagen with the DNA molecule modifies its physicochemical properties, and, second, direct incorporation of the mutagen within the primary structure of the molecule alters the base sequence. Physical mutagens, like X-irradiation and ultraviolet rays, are known to block DNA synthesis in vivo and in vitro and to cause alterations in DNA structure (see Chapter 12). 

With the growing number of proteins sequenced, there is a necessity for novel techniques to analyze protein sequences in order to determine their structure and function. The most commonly used protein sequence descriptors are based on evolutionary information and physicochemical properties. Even though these methods have proven to be efficient in most cases, in cases of transmembrane proteins, they may fall short. As the vast field of transmembrane proteins largely remains unexplored with many transmembrane proteins yet to be sequenced, it is possible to obtain new protein sequences without any known homolog. In such cases, traditional sequence analysis methods based on alignment profiles would not be sufficient. The evolutionary information-based descriptors appear inadequate, and indices based on physicochemical property can cause ambiguities. Therefore, it is of considerable interest to develop novel methods based on sequence information alone to represent protein sequences. 

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