WITHDRAWN: An insightful recollection since the distorted key theory was born about 23 years ago

Abstract

During the last three decades or so, many efforts have been made to study the protein cleavage sites by some disease-causing enzyme, such as HIV (human immunodeficiency virus) protease and SARS (severe acute respiratory syndrome) coronavirus main proteinase. It has become increasingly clear via this minireview that the motivation driving the aforementioned studies is quite wise, and that the results acquired through these studies are very rewarding, particularly for developing peptide drugs. Running Title: Recollection of distorted key theoryJournal Pre-proof J o u r n a l P r e -p r o o f Furthermore, a web-server called "HIVcleave" [21] has been established for predicting HIV protease cleavage sites in proteins. Its website address is at Just like the pseudo amino acid components [51-54] and the 5-steps rule [55], which have been stimulated by the development of the sequence bioinformatics, widely and increasingly used in proteome and genome analysis and , it is anticipated that the "distorted key theory" that was stimulated from the structural bioinformatics [187] as well as some pioneering studies [188][189][190][191][192][193][194][195] and their follow-up studies , will be also widely and increasingly used in drug development, particularly for developing peptide drugs [217] and multi-target drugs [218]. Journal Pre-proof J o u r n a l P r e -p r o o f Journal Pre-proof J o u r n a l P r e -p r o o f 5 Figure 1 Journal Pre-proof J o u r n a l P r e -p r o o f 6 Figure 2. A schematic illustration to show a peptide in good fitting and tightly binding with the enzyme's active site before it is cleaved by the latter. Adapted from [42] with permission.

Using Chou’s 5-Step Rule to Evaluate the Stability of Tautomers: Susceptibility of 2-[(Phenylimino)-methyl]-cyclohexane-1,3-diones to Tautomerization Based on the Calculated Gibbs Free Energies

“…The advantages of this principle are: logic and transparency in action, the possibility for other researchers to repeat research, ease in developing methods and improving shortcomings, and, most importantly, convenience for use by other researchers. Therefore, the role of Chou's 5-step method in conducting proteome/genome analyses, drug development, and research on bioorganic compounds, is unusual and amazing [61][62][63][64][65][66][67][68][69][70][71].…”

South Atlantic Anomaly, Ionospheric Signals from Seismic Events

“…Although at the present the reports in this regard from theoretical scientists are more than those from experimental scientists, it is anticipated that, with more experimental data available in future, this kind of reports from experimental scientists will be increasing as well. Particularly, the combined reports between experimental and theoretical approaches, or their compliments to each other, will increasingly appear, as indicated by some very impressive papers [35][36][37][38][39][40][41] and a series of very recent papers (see, e.g., [42][43][44][45][46][47][48][49][50][51][52][53][54][55][56]).…”

The pLoc_bal-mGneg Predictor is a Powerful Web-Server for Identifying the Subcellular Localization of Gram-Negative Bacterial Proteins based on their Sequences Information Alone

“…For the amazing and awesome roles of the "5-steps rule" and general "PseAAC" in driving proteome, genome analyses and drug development, see a series of recent papers [2,93,[223][224][225][226][227][228][229][230][231][232][233] where both the "5steps rule" and the general "PseAAC" as well as their huge impacts have been very impressively recollected at different angles or from varieties of aspects.…”