Guide Unfolding Islam

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  1. Signs on the Earth | The Muslim
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Some take refuge in the supernatural, saying that Allah did not allow error to be sanctioned by the community. None of these arguments was considered decisive in the Third Century of Islam, when there was still fierce debate on such matters. Muslims should not fear the application of modern historical methods to Islam, for they possess something that is missing from every other classical religion: a contemporary record of the teaching of their Founder.

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In the course of this book, I present detailed evidence, mainly from the Koran itself, for the contention that the consonantal text is more or less exactly as it was written down in the lifetime of the Prophet. There are small differences, mainly in pronunciation, but these hardly ever make any difference to the meaning, and they were recognized and catalogued by Muslim scholars eleven or twelve centuries ago. Western scholars have been examining manuscripts of the Koran for two centuries without finding any significant departures from the received consonantal text - and it would need only one authentic page from one deviant version to demolish faith in the whole concept of an authentic text.

Some scholars still claim that the Koran was written long after the death of Muhammad, but this is simply preposterous.

Signs on the Earth | The Muslim

The latest possible date for getting agreement from all Muslims was 24 years after he died, since that is when relations broke down permanently between Sunni and Shia. Both factions, soon joined by a third, the Kharijites, would have dearly loved to possess a Koran that backed their claims against those of their opponents, yet all accept the same text.

The same events that guarantee the authenticity of the Koran require us to be very cautious in using the later literature, all of which was transmitted orally during generations of warfare and repression. The descendants of the Prophet's Companions were all keen to show that their ancestors had been virtuous and that the descent into civil war was the fault of others. Soon there came to be also an urgent need for precedents to establish particular interpretations of Islam, and these could only be accepted if they could be attributed to the Prophet and those who had known him.

Alanines are shown in black, and the other residues are in gray. Figure S1. The symbols represent the experimental data and the continuous lines represent two-state model fitted curves. The pH values are 4. Thermal denaturation curves, measured with DSC, were all cooperative and two-state, typical of a small natively folded protein with a densely packed interior Fig. Substitution with alanine slightly reduced the melting temperature T m of the variants, as anticipated. This increase in enthalpy was counter-intuitive, because we imagined that the substitution of bulky residues with the small alanine side-chain would create voids, thus reducing the van der Waals interactions between side-chain atoms and consequently the enthalpy of denaturation.

Figure S2b , slightly reducing the melting temperatures Suppl. Figure S2a ; Table 2 ; and Suppl. Table S1. The thermodynamic parameters determined from DSC thermographs are mentioned. Values for BPTI and 25 are estimates, not experimentally determined. The reported errors are fitting errors computed by analyzing a single DSC curve at pH4.

An alternate calculation based on a multi-linear equation is reported in Suppl. To provide a structural view of this peculiar instance of enthalpy stabilization, we crystallized and solved the structures of six simplified BPTI variants containing 19, 20, 21, 22, 23, and 24 alanines Fig. On the other hand, despite repeated trials, BPTI variants containing 25—27 alanines merely formed needle crystals, unsuitable for diffraction. All six variants crystallized under the same conditions, indicating a minimal disturbance of the surface properties, even upon multiple alanine substitutions.

In all of the structures, the overall backbone and side-chain conformations were almost perfectly retained, with a backbone root square mean deviation RMSD of 0. Figure S3. Therefore, despite the large number of alanine substitutions, the native-like backbone structure and the densely packed protein interior remained completely unaffected Fig.

Figure S4. Alanines are shown as blue spheres in surface model. Spheres represent water molecules around the alanine substitution sites. In panels b-d the alanines as well as the residues substituted to alanines are encircled. The side-chain conformations of almost all residues were retained in all simplified BPTIs, indicating that multiple alanine substitutions did not affect the native-like densely packed protein interior. For the purpose of discussion, we examined the fine structural changes induced near the substitution sites by the mutations.

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The R39A substitution also recruited 1—2 new water molecules close to the amide nitrogen of Ala 39 , extending the hydration networks observed in BPTIA. Similarly, the P8A substitution did not affect the local structure, but recruited a water molecule and a sulfate ion, which formed new hydrogen bonds with the amide nitrogen of Ala 8 Fig. Finally, both the intramolecular hydrogen bonds and the hydration structures at other positions were essentially unchanged from those in the wild-type BPTIs Suppl.

Alanine substitutions introduced in this study are mentioned on the left of the panel and BPTI variants are indicated at the top of the panel. Inter-atomic distances between backbone atoms amide nitrogen and carbonyl oxygen and water molecules are mentioned in Angstrom. Arrows indicate the direction of the hydrogen bonds, from donor to acceptor atoms. The number of protein-water hydrogen bonds increased at and around the substitution sites with increasing number of alanine substitutions.

At sites far from the alanine substitutions the hydrogen bonding and hydration structures remained unchanged Suppl. Protein-water hydrogen bonds were calculated using HBAT Let us consider possible structural features that could account for the increase in enthalpy change arising from the multiple alanine substitutions Fig.

ISBN 13: 9781859640463

X-ray crystallographic analyses indicated that all of the simplified BPTI structures fully overlapped Fig. Correlation coefficients are shown within the panel. Water molecules residing within 3. In panel d, we considered 5pti, 6pti and 7pti structures as wild-type BPTI and for the simplified variants we included all the chains monomers in their asymmetric unit.

Similar correlation was also observed in specific entropy versus hydration structures plot Suppl. Figure S5. Generally, an increase in entropy change is interpreted as either an enlargement of the conformational space in the denatured state or as a loss of it in the native state, in which both the chain and hydration terms must be accounted for.

We first imagined that replacing bulky side chains with small alanine side chains would create voids, increasing the flexibility of the local chain in the native state, and thus reducing the entropy of unfolding, and consequently stabilizing the native state in terms of entropy. Another possibility being that the entropy of the denatured state increases by reducing the size of side-chains and thus increasing the conformational space of the denatured state, which would destabilize the native state.

DSC experiments indicated that the entropy of unfolding increased upon replacement of the native amino acids with increasing number of alanine replacements.

Moreover, the crystal structures indicated that the voids were filled with water molecules and the flexibility or dynamics of the residues surrounding the mutations were unchanged, as assessed with the B-factors Suppl. The entropy destabilization observed upon alanine substitution may thus originate from the enlargement of the conformational space in the denatured state. The difference could be accounted for by entropy loss associated with the increased number of water molecules released to the bulk water upon the denaturation of the simplified BPTIs Fig.

Finally, a strong correlation between the number of protein—water hydrogen bonds Fig. In principle, measuring the thermodynamics of mutants where a large buried hydrophobic residue is replaced to alanine could provide further proof of this effect, however, such substitutions nearly completely unfold BPTI-[5,55] 16 making such analysis impractical.

The enthalpy stabilization introduced to a protein with multiple alanine substitutions is novel and unexpected. A comparison of the thermodynamic parameters and structural data suggests that the enthalpy stabilization of the simplified BPTIs probably arises from improved interactions between water molecules and the protein.

Further analyses, such as DSC performed with D 2 O protein solutions might enable decomposition of water contribution to electrostatic and hydrogen-bonding terms. The rational design of enthalpy stabilization usually requires high-resolution structures for designing novel hydrogen bonds 17 or salt bridges 18 to fill cavities 19 or to relax steric clashes 11 , 12 , which is difficult.

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Product Highlights Set in the context of the geography and history of what may be called the super-continent of Afro- Eurasia, the book centers on the Koran and the life of the Prophet Muhammad and his companions, showing how later developments are rooted there, right down to questions of contemporary relevance such as the difference between Sunni Muslims and Shiites, Sufis and literalists, reformists and 'fundamentalists'.

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